Science.gov

Sample records for agt federal deregulation

  1. Electric utility mergers: Competition, deregulation and the evolving federal policy

    NASA Astrophysics Data System (ADS)

    Patton, David Baird

    As the electric utility industry moves from a regulated monopoly structure to a deregulated competitive market, horizontal and vertical merger activity has increased substantially. The Federal Energy Regulatory Commission ("FERC") generally takes the lead at the federal level for reviewing the competitive effects of electric utility mergers. Shortly after it issued its order open access order requiring utilities to allow others to use their transmission systems in 1996, FERC issued a merger policy statement outlining a new analytic approach that more accurately reflects the physical and economic realities of competition in a deregulated electric industry. This study will critically examine the federal merger review process and policies seeking to determine whether (1) the Commission's methodology provides an accurate and reliable measure of the effects of a merger on competition, (2) the market power remedies that the Commission has required from merger applicants mitigate potential market power and improve economic efficiency, and (3) transactions costs provide an alternative explanation for horizontal electric utility mergers. In addition to the economic analysis of these issues, the study includes an empirical analysis of the effects of three recent mergers.

  2. AGT100 turbomachinery. [for automobiles

    NASA Technical Reports Server (NTRS)

    Tipton, D. L.; Mckain, T. F.

    1982-01-01

    High-performance turbomachinery components have been designed and tested for the AGT100 automotive engine. The required wide range of operation coupled with the small component size, compact packaging, and low cost of production provide significant aerodynamic challenges. Aerodynamic design and development testing of the centrifugal compressor and two radial turbines are described. The compressor achieved design flow, pressure ratio, and surge margin on the initial build. Variable inlet guide vanes have proven effective in modulating flow capacity and in improving part-speed efficiency. With optimum use of the variable inlet guide vanes, the initial efficiency goals have been demonstrated in the critical idle-to-70% gasifier speed range. The gasifier turbine exceeded initial performance goals and demonstrated good performance over a wide range. The radial power turbine achieved 'developed' efficiency goals on the first build.

  3. AGT (Advanced Gas Turbine) technology project

    NASA Technical Reports Server (NTRS)

    1988-01-01

    An overall summary documentation is provided for the Advanced Gas Turbine Technology Project conducted by the Allison Gas Turbine Division of General Motors. This advanced, high risk work was initiated in October 1979 under charter from the U.S. Congress to promote an engine for transportation that would provide an alternate to reciprocating spark ignition (SI) engines for the U.S. automotive industry and simultaneously establish the feasibility of advanced ceramic materials for hot section components to be used in an automotive gas turbine. As this program evolved, dictates of available funding, Government charter, and technical developments caused program emphases to focus on the development and demonstration of the ceramic turbine hot section and away from the development of engine and powertrain technologies and subsequent vehicular demonstrations. Program technical performance concluded in June 1987. The AGT 100 program successfully achieved project objectives with significant technology advances. Specific AGT 100 program achievements are: (1) Ceramic component feasibility for use in gas turbine engines has been demonstrated; (2) A new, 100 hp engine was designed, fabricated, and tested for 572 hour at operating temperatures to 2200 F, uncooled; (3) Statistical design methodology has been applied and correlated to experimental data acquired from over 5500 hour of rig and engine testing; (4) Ceramic component processing capability has progressed from a rudimentary level able to fabricate simple parts to a sophisticated level able to provide complex geometries such as rotors and scrolls; (5) Required improvements for monolithic and composite ceramic gas turbine components to meet automotive reliability, performance, and cost goals have been identified; (6) The combustor design demonstrated lower emissions than 1986 Federal Standards on methanol, JP-5, and diesel fuel. Thus, the potential for meeting emission standards and multifuel capability has been initiated

  4. Confronting Deregulation.

    ERIC Educational Resources Information Center

    Madget, James

    1997-01-01

    Discusses how schools can capitalize on new opportunities for cost savings and improved service in a deregulated electric industry. It discusses strategies for preparing to buy electrical power on the open market and examines two forms of purchasing called "wholesale-wheeling" and "retail-wheeling." Steps in conducting a…

  5. Advanced Gas Turbine (AGT) powertrain system development for automotive applications

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A gas turbine powertrain for automobiles with reduced fuel consumption and reduced environmental impact is investigated. The automotive gas turbine, when installed in an automobile (3000 pounds inertia weight), provides a CFDC fuel economy of 42.8 miles per gallon based on EPA test procedures and diesel No. 2 fuel. The AGT powered vehicle substantially gives the same overall vehicle driveability and performance as a comparable production vehicle powered by a conventional spark ignition powertrain system. The emissions are less than federal standards, and a variety of fuels can be used.

  6. Advanced Gas Turbine (AGT) technology development project

    NASA Technical Reports Server (NTRS)

    1987-01-01

    This report is the final in a series of Technical Summary Reports for the Advanced Gas Turbine (AGT) Technology Development Project, authorizrd under NASA Contract DEN3-167 and sponsored by the DOE. The project was administered by NASA-Lewis Research Center of Cleveland, Ohio. Plans and progress are summarized for the period October 1979 through June 1987. This program aims to provide the US automotive industry the high risk, long range technology necessary to produce gas turbine engines for automobiles that will reduce fuel consumption and reduce environmental impact. The intent is that this technology will reach the marketplace by the 1990s. The Garrett/Ford automotive AGT was designated AGT101. The AGT101 is a 74.5 kW (100 shp) engine, capable of speeds to 100,000 rpm, and operates at turbine inlet temperatures to 1370 C (2500 F) with a specific fuel consumption level of 0.18 kg/kW-hr (0.3 lbs/hp-hr) over most of the operating range. This final report summarizes the powertrain design, power section development and component/ceramic technology development.

  7. Changing Public Interest Values in Broadcast Deregulation.

    ERIC Educational Resources Information Center

    Virts, Paul H.

    Because the Federal Communication Commission's (FCC) decision to deregulate commercial radio has created great controversy over what constitutes "public interest" in broadcast deregulation, this paper provides a brief historical analysis of the bases for defining the public interest standard in broadcast regulation and examines the use…

  8. AGT 100 automotive gas turbine system development

    NASA Technical Reports Server (NTRS)

    Helms, H. E. G.

    1982-01-01

    General Motors is developing an automotive gas turbine system that can be an alternate powerplant for future automobiles. Work sponsored by DOE and administered by NASA Lewis Research Center is emphasizing small component aerodynamics and high-temperature structural ceramics. Reliability requirements of the AGT 100 turbine system include chemical and structural ceramic component stability in the gas turbine environment. The power train system, its configuration and schedule are presented, and its performance tested. The aerodynamic component development is reviewed with discussions on the compressor, turbine, regenerator, interturbine duct and scroll, and combustor. Ceramic component development is also reviewed, and production cost and required capital investment are taken into consideration.

  9. Advanced Gas Turbine (AGT) powertrain system development for automotive applications

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Topics covered include the AGT 101 engine test; compressor design modification; cold air turbine testing; Mod 1 alloy turbine rotor fabrication; combustion aspects; regenerator development; and thermal screening tests for ceramic materials. The foil gas bearings, rotor dynamics, and AGT controls and accessories are also considered.

  10. AGT and the Segal-Sugawara construction

    NASA Astrophysics Data System (ADS)

    Carlsson, Erik

    2017-01-01

    The conjectures of Alday et al. [Lett. Math. Phys. 91, 167-197 (2010)] and their generalizations have been mathematically formulated as the existence of an action of a W-algebra on the cohomology or K-theory of the instanton moduli space, together with a Whitaker vector [A. Braverman et al., e-print arXiv:1406.2381 (2014); D. Maulik and A. Okounkov, e-print arXiv:1211.1287 (2012), pp. 1-276; O. Schiffmann and E. Vasserot, Publ. Math. Inst. Hautes Etud. Sci. 118, 213-342 (2013)]. However, the original conjectures also predict intertwining properties with the natural higher rank version of the "Ext1 operator" which was previously studied by Okounkov and the author in Carlsson and Okounkov [Duke Math. J. 161, 1797-1815 (2012)], a result which is now sometimes referred to as AGT in rank one [A. Alba et al., Lett. Math. Phys. 98, 33-64 (2011); M. Pedrini et al., J. Geom. Phys. 103, 43-89 (2016)]. Physically, this corresponds to incorporating matter in the Nekrasov partition functions, an obviously important feature in the physical theory. It is therefore of interest to study how the Ext1 operator relates to the aforementioned structures on cohomology in higher rank, and if possible to find a formulation from which the AGT conjectures follow as a corollary. In this paper, we carry out something analogous using a modified Segal-Sugawara construction for the s l ˆ 2 C structure that appears in Nekrasov and Okounkov [Prog. Math. 244, 525-596 (2006)] for general rank. This immediately implies the AGT identities when the central charge is one, a case which is of particular interest for string theorists, and because of the natural appearance of the Seiberg-Witten curve in this setup, see, for instance, Dijkgraaf and Vafa [e-print arXiv:0909.2453 (2009).] as well as Iqbal et al. [J. High Energy Phys. 2009, 69].

  11. AGT101 automotive gas turbine system development

    NASA Technical Reports Server (NTRS)

    Rackley, R. A.; Kidwell, J. R.

    1982-01-01

    The AGT101 automotive gas turbine system consisting of a 74.6 kw regenerated single-shaft gas turbine engine, is presented. The development and testing of the system is reviewed, and results for aerothermodynamic components indicate that compressor and turbine performance levels are within one percent of projected levels. Ceramic turbine rotor development is encouraging with successful cold spin testing of simulated rotors to speeds over 12,043 rad/sec. Spin test results demonstrate that ceramic materials having the required strength levels can be fabricated by net shape techniques to the thick hub cross section, which verifies the feasibility of the single-stage radial rotor in single-shaft engines.

  12. The AGT 101 advanced automotive gas turbine

    NASA Technical Reports Server (NTRS)

    Rackley, R. A.; Kidwell, J. R.

    1982-01-01

    A development program is described whose goal is the accumulation of the technology base needed by the U.S. automotive industry for the production of automotive gas turbine powertrains. Such gas turbine designs must exhibit reduced fuel consumption, a multi-fuel capability, and low exhaust emissions. The AGT101 powertrain described is a 74.6 kW, regenerated single-shaft gas turbine, operating at a maximum inlet temperature of 1644 K and coupled to a split differential gearbox and automatic overdrive transmission. The engine's single stage centrifugal compressor and single stage radial inflow turbine are mounted on a common shaft, and will operate at a maximum rotor speed of 100,000 rpm. All high temperature components, including the turbine rotor, are ceramic.

  13. Advanced Gas Turbine (AGT) technology report

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Engine testing, ceramic component fabrication and evaluation, component performance rig testing, and producibility experiments at Pontiac comprised AGT 100 activities of this period, January to December 1984. Two experimental engines were available and allowed the evaluation of eight experimental assemblies. Operating time accumulated was 115 hr of burning and 156 hr total. Total cumulative engine operating time is now 225 hr. Build number 11 and 12 of engine S/N 1 totaled 28 burning hours and constituted a single assembly of the engine core--the compressor, both turbines, and the gearbox. Build number 11 of engine S/N 1 included a 1:07 hr continuous test at 100% gasifier speed (86,000 rpm). Build number 8 of engine S/N 2 was the first engine test with a ceramic turbine rotor. A mechanical loss test of an engine assembly revealed the actual losses to be near the original design allowance. Component development activity included rig testing of the compressor, combustor, and regenerator. Compressor testing was initiated on a rig modified to control the transfer of heat between flow path, lubricating oil, and structure. Results show successful thermal decoupling of the rig and lubricating/cooling oil. Rig evaluation of a reduced-friction compressor was initiated. Combustor testing covered qualification of ceramic parts for engine use, mapping of operating range limits, and evaluation of a relocated igniter plug. Several seal refinements were tested on the hot regenerator rig. An alternate regenerator disk, extruded MAS, was examined and found to be currently inadequate for the AGT 100 application. Also, a new technique for measuring leakage was explored on the regenerator rig. Ceramic component activity has focused on the development of state-of-the-art material strength characteristics in full-scale hardware. Injection-molded sintered alpha-SiC rotors were produced at Carborundum in an extensive process and tool optimization study.

  14. Recombinant human O6-alkylguanine-DNA alkyltransferase (AGT), Cys145-alkylated AGT and Cys145 --> Met145 mutant AGT: comparison by isoelectric focusing, CD and time-resolved fluorescence spectroscopy.

    PubMed Central

    Federwisch, M; Hassiepen, U; Bender, K; Dewor, M; Rajewsky, M F; Wollmer, A

    1997-01-01

    Isoelectric focusing, CD, steady-state and time-resolved fluorescence spectroscopy were used to compare the native recombinant human DNA-repair protein O6-alkylguanine-DNA alkyltransferase (AGT) with AGT derivatives methylated or benzylated on Cys145 or modified by site-directed mutagenesis at the active centre (Met145 mutant). The AGT protein is approximately spherical with highly constrained Trp residues, but is not stabilized by disulphide bridges. In contrast with native AGT, alkylated AGT precipitated at 25 degrees C but remained monomeric at 4 degrees C. As revealed by isoelectric focusing, pI changed from 8.2 (AGT) to 8. 4 (Cys145-methylated AGT) and 8.6 (Cys145-benzylated AGT). The alpha-helical content of the Met145 mutant was decreased by approx. 5% and Trp residues were partially liberated. Although non-covalent binding of O6-benzylguanine did not alter the secondary structure of AGT, its alpha-helical content was increased by approx. 2% on methylation and by approx. 4% on benzylation, altogether indicating a small conformational change in AGT on undergoing alkylation. No signal sequences have been found in AGT that mark it for polyubiquitination. Therefore the signal for AGT degradation remains to be discovered. PMID:9164873

  15. Advanced Gas Turbine (AGT) Technology Development Project

    NASA Technical Reports Server (NTRS)

    1987-01-01

    This report is the eleventh in the series of Technical Summary reports for the Advanced Gas Turbine (AGT) Technology Development Project, authorized under NASA Contract DEN3-167, and sponsored by the Department of Energy (DOE). This report was prepared by Garrett Turbine Engine Company, A Division of the Garrett Corporation, and includes information provided by Ford Motor Company, the Standard Oil Company, and AiResearch Casting Company. This report covers plans and progress for the period July 1, 1985 through June 30, 1986. Technical progress during the reported period was highlighted by the 85-hour endurance run of an all-ceramic engine operating in the 2000 to 2250 F temperature regime. Component development continued in the areas of the combustion/fuel injection system, regenerator and seals system, and ceramic turbine rotor attachment design. Component rig testing saw further refinements. Ceramic materials showed continued improvements in required properties for gas turbine applications; however, continued development is needed before performance and reliability goals can be set.

  16. Advanced Gas Turbine (AGT) Technology Project

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Engine testing, ceramic component fabrication and evaluation, component performance rig testing, and analytical studies comprised AGT 100 activities during the 1985 year. Ten experimental assemblies (builds) were evaluated using two engines. Accrued operating time was 120 hr of burning and 170 hr total, bringing cumulative total operating time to 395 hr, all devoid of major failures. Tests identified the generator seals as the primary working fluid leakage sources. Power transfer clutch operation was demonstrated. An alpha SiC gasifier rotor engine test resulted in blade tip failures. Recurring case vibration and shaft whip have limited gasifier shaft speeds to 84%. Ceramic components successfully engine tested now include the SiC scroll assembly, Si3N3 turbine rotor, combustor assembly, regenerator disk bulkhead, turbine vanes, piston rings, and couplings. A compressor shroud design change to reduce heat recirculation back to the inlet was executed. Ceramic components activity continues to focus on the development of state-of-the-art material strength characteristics in full-scale engine hardware. Fiber reinforced glass-ceramic composite turbine (inner) backplates were fabricated by Corning Glass Works. The BMAS/III material performed well in engine testing. Backplates of MAS material have not been engine tested.

  17. Advanced Gas Turbine (AGT) Technology Development Project, ceramic component developments

    NASA Technical Reports Server (NTRS)

    Teneyck, M. O.; Macbeth, J. W.; Sweeting, T. B.

    1987-01-01

    The ceramic component technology development activity conducted by Standard Oil Engineered Materials Company while performing as a principal subcontractor to the Garrett Auxiliary Power Division for the Advanced Gas Turbine (AGT) Technology Development Project (NASA Contract DEN3-167) is summarized. The report covers the period October 1979 through July 1987, and includes information concerning ceramic technology work categorized as common and unique. The former pertains to ceramic development applicable to two parallel AGT projects established by NASA contracts DEN3-168 (AGT100) and DEN3-167 (AGT101), whereas the unique work solely pertains to Garrett directed activity under the latter contract. The AGT101 Technology Development Project is sponsored by DOE and administered by NASA-Lewis. Standard Oil directed its efforts toward the development of ceramic materials in the silicon-carbide family. Various shape forming and fabrication methods, and nondestructive evaluation techniques were explored to produce the static structural components for the ceramic engine. This permitted engine testing to proceed without program slippage.

  18. Overview: Tuition Deregulation

    ERIC Educational Resources Information Center

    Texas Higher Education Coordinating Board, 2009

    2009-01-01

    Prior to 2003, the Texas Legislature had the regulatory authority to set tuition rates, generally mandating that the same statutory and designated tuition rate be charged across the state. Tuition deregulation became effective September 1, 2003, and universities began increasing designated tuition in spring 2004. This article answers the following…

  19. Ceramics for the AGT101 automotive gas turbine

    NASA Technical Reports Server (NTRS)

    Kreiner, D. M.; Wimmer, J. M.

    1981-01-01

    An advanced gas turbine powertrain for automotive application is being developed. Objectives of the program include a fuel consumption of 42.8 mpg on No. 2 diesel fuel in a 3000 pound car, same overall vehicle performance as obtained with a conventional spark ignition internal combustion engine, low emission, multiple fuel capacity, reliability, and competitive cost. The AGT101 powertrain consists of a power section, gearbox and transmission, and the design and analysis conducted thus far support the initial engine concept, as no significant design changes have been required. The ceramic rotor design approach and component materials are discussed, and it is projected that the AGT powertrain will be competitive with any other alternative powertrain in meeting the design objectives.

  20. Field testing advanced geothermal turbodrill (AGT). Phase 1 final report

    SciTech Connect

    Maurer, W.C.; Cohen, J.H.

    1999-06-01

    Maurer Engineering developed special high-temperature geothermal turbodrills for LANL in the 1970s to overcome motor temperature limitations. These turbodrills were used to drill the directional portions of LANL`s Hot Dry Rock Geothermal Wells at Fenton Hill, New Mexico. The Hot Dry Rock concept is to drill parallel inclined wells (35-degree inclination), hydraulically fracture between these wells, and then circulate cold water down one well and through the fractures and produce hot water out of the second well. At the time LANL drilled the Fenton Hill wells, the LANL turbodrill was the only motor in the world that would drill at the high temperatures encountered in these wells. It was difficult to operate the turbodrills continuously at low speed due to the low torque output of the LANL turbodrills. The turbodrills would stall frequently and could only be restarted by lifting the bit off bottom. This allowed the bit to rotate at very high speeds, and as a result, there was excessive wear in the bearings and on the gauge of insert roller bits due to these high rotary speeds. In 1998, Maurer Engineering developed an Advanced Geothermal Turbodrill (AGT) for the National Advanced Drilling and Excavation Technology (NADET) at MIT by adding a planetary speed reducer to the LANL turbodrill to increase its torque and reduce its rotary speed. Drilling tests were conducted with the AGT using 12 1/2-inch insert roller bits in Texas Pink Granite. The drilling tests were very successful, with the AGT drilling 94 ft/hr in Texas Pink Granite compared to 45 ft/hr with the LANL turbodrill and 42 ft/hr with a rotary drill. Field tests are currently being planned in Mexico and in geothermal wells in California to demonstrate the ability of the AGT to increase drilling rates and reduce drilling costs.

  1. Advanced Gas Turbine (AGT) Technology Development Project annual report

    NASA Technical Reports Server (NTRS)

    1986-01-01

    This report is the tenth in a series of Technical Summary reports for the Advanced Gas Turbine (AGT) Technology Development Project, authorized under NASA Contract DEN3-167, and sponsored by the Department of Energy (DOE). This report was prepared by Garrett Turbine Engine Company, A Division of the Garrett Corporation, and includes information provided by Ford Motor Company, the Carborundum Company, and AiResearch Casting Company. The Project is administered by Mr. Thomas N. Strom, Project Manager, NASA-Lewis Research Center, Cleveland, Ohio. This report covers plans and progress for the period July 1, 1984 through June 30, 1985.

  2. AGT relations for abelian quiver gauge theories on ALE spaces

    NASA Astrophysics Data System (ADS)

    Pedrini, Mattia; Sala, Francesco; Szabo, Richard J.

    2016-05-01

    We construct level one dominant representations of the affine Kac-Moody algebra gl̂k on the equivariant cohomology groups of moduli spaces of rank one framed sheaves on the orbifold compactification of the minimal resolution Xk of the Ak-1 toric singularity C2 /Zk. We show that the direct sum of the fundamental classes of these moduli spaces is a Whittaker vector for gl̂k, which proves the AGT correspondence for pure N = 2 U(1) gauge theory on Xk. We consider Carlsson-Okounkov type Ext-bundles over products of the moduli spaces and use their Euler classes to define vertex operators. Under the decomposition gl̂k ≃ h ⊕sl̂k, these vertex operators decompose as products of bosonic exponentials associated to the Heisenberg algebra h and primary fields of sl̂k. We use these operators to prove the AGT correspondence for N = 2 superconformal abelian quiver gauge theories on Xk.

  3. National policy in a deregulated marketplace

    SciTech Connect

    Jensen, V.

    1996-12-31

    This paper is one of three keynote presentations given at the conference. It briefly discusses government policy issues regarding electric utility deregulation. Three major questions are examined: (1) policies and institutions required to ensure a free market, (2) allocation of stranded assets and ensuring that consumers benefit from restructuring, and (3) continuation of collateral utility activities such as low income program investments, energy efficiency, and renewable energy use. Types of policy options under consideration are reviewed, and potential state and federal roles are described.

  4. Advanced Gas Turbine (AGT) powertrain system development for automotive applications

    NASA Technical Reports Server (NTRS)

    1981-01-01

    An automotive gas turbine powertrain system which, when installed in a 1985 production vehicle (3000 pounds inertia weight), is being developed with a CFDC fuel economy of 42.8 miles per gallon based on Environmental Protection Agency (EPA) test procedures and diesel No. 2 fuel. The AGT-powered vehicle shall give substantially the same overall vehicle driveability and performance as a comparable 1985 production vehicle powered by a conventional spark ignition powertrain system (baseline system). Gaseous emissions and particulate levels less than: NOx = 0.4 gm/mile, HC = 0.41 gm/mile, and CO = 3.4 gm/mile, and a total particulate of 0.2 gm/mile, using the same fuel as used for fuel economy measurements is expected, along with the ability to use a variety of alternate fuels.

  5. Advanced Gas Turbine (AGT) powertrain system development for automotive applications

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Progress in the development of a gas turbine engine to improve fuel economy, reduce gaseous emissions and particulate levels, and compatible with a variety of alternate fuels is reported. The powertrain is designated AGT101 and consists of a regenerated single shaft gas turbine engine, a split differential gearbox and a Ford Automatic Overdrive production transmission. The powertrain is controlled by an electronic digital microprocessor and associated actuators, instrumentation, and sensors. Standard automotive accessories are driven by engine power provided by an accessory pad on the gearbox. Component/subsystem development progress is reported in the following areas: compressor, turbine, combustion system, regenerator, gearbox/transmission, structures, ceramic components, foil gas bearing, bearings and seals, rotor dynamics, and controls and accessories.

  6. Generalized Rogers Ramanujan Identities Motivated by AGT Correspondence

    NASA Astrophysics Data System (ADS)

    Belavin, Alexander A.; Gepner, Doron R.

    2013-12-01

    AGT correspondence and its generalizations attracted a great deal of attention recently. In particular, it was suggested that U( r) instantons on describe the conformal blocks of the coset , where n is a parameter. It has been shown that the representations of algebra A( r, p) n for generic values n possesses the distinguished geometrical bases. It is interesting to consider the case when the parameter n is integer. We will concentrate on this case and describe Generalized Rogers Ramanujan (GRR) identities for these cosets, which expresses the characters as certain q series. We propose that such identities exist for the coset A( r, p) n for all positive integers n and all r and p. We treat here the case of n = 1 and r = 2, finding GRR identities for all the characters.

  7. Deregulation and the American Education Marketplace

    ERIC Educational Resources Information Center

    Dorsey, Dana N. Thompson; Plucker, Jonathan A.

    2016-01-01

    The deregulation movement has impacted the social, political, and economic landscape in the United States and continues to do so. In this article, we briefly summarize the general history of deregulation in this country and the meaning of deregulation within the specific context of education policy and reform. We focus on deregulation efforts…

  8. The Impact of Television Deregulation on Private and Public Interests.

    ERIC Educational Resources Information Center

    Ferrall, Victor E., Jr.

    1989-01-01

    Examines the impact of six years (1981-1987) of television deregulation by the United States Federal Communications Commission (FCC). Contends that the FCC's rule deletions have altered economic relations among segments of the television industry and its users, and discusses effects on the future of "free" television. (MS)

  9. Electrical Energy Service Options: Deregulation Presents New Opportunities.

    ERIC Educational Resources Information Center

    Matterson, Gary C.

    1995-01-01

    It is noted that federal deregulation of the electrical utility industry will allow colleges and universities to buy electrical services from suppliers who provide the best reliability and cost combination. Considerations are examined for the following options: purchasing an existing electrical substation, building a new substation, using on-site…

  10. State Deregulation and Management Flexibility.

    ERIC Educational Resources Information Center

    Tancredo, Thomas G.; And Others

    1984-01-01

    The origin of deregulation of higher education in Colorado, its effects, and implications for other states are discussed. In "How and Why It Happened," Thomas G. Tancredo traces the development of a new budgeting process, called MOU (memorandum of understanding). Under MOU each governing board is responsible for setting the expenditure…

  11. Deregulation? Early Radio Policy Reconsidered.

    ERIC Educational Resources Information Center

    Benjamin, Louise M.

    In debating the merits of the deregulation of broadcasting, policy makers should be cognizant of the conditions that led originally to that regulation. An examination of (1) the letters and speeches of Secretary of Commerce, Herbert Hoover, the first regulator of broadcasting; (2) the congressional debate over the regulatory issues of monopoly,…

  12. A technology development summary for the AGT101 advanced gas turbine program

    NASA Technical Reports Server (NTRS)

    Boyd, Gary L.; Kidwell, James R.; Kreiner, Daniel M.

    1987-01-01

    A summary is presented of significant technology developments that have been made in the AGT101 advanced gas turbine program. The AGT101 design features are reviewed, and the power section testing and results are addressed in detail. The results of component testing and evaluation are described for the compressor, turbine, regenerator, and foil bearing. Ceramic component development is discussed, including that of the static seal, turbine shroud seal, regenerator shield planar seal, regenerator shield piston ring, stator rig, ceramic combustor, and turbine rotor. Important areas to be addressed by the Advanced Turbine Technology Applications Project now in the planning stage at DOE and NASA are briefly reviewed.

  13. Effects of microRNA-29a on retinopathy of prematurity by targeting AGT in a mouse model

    PubMed Central

    Chen, Xin-Ke; Ouyang, Li-Juan; Yin, Zheng-Qin; Xia, Yuan-You; Chen, Xiu-Rong; Shi, Hui; Xiong, Yan; Pi, Lian-Hong

    2017-01-01

    Background: This study aimed to explore the effects of microRNA-29a (miR-29a) on retinopathy of prematurity (ROP) by targeting angiotensinogen (AGT) expression in a mouse model. Methods: Ninety-six C57BL/6J mice were selected and divided into the normal control group (n = 12) and the oxygen-induced retinopathy (OIR) group (n = 84). All the mice in the OIR group were assigned to the following seven groups (12 mice in each group): the blank, miR-29a mimics, miR-29a inhibitors, empty plasmid, miR-29a mimics + si-AGT, miR-29a inhibitors + si-AGT and si-AGT groups. ADPase histochemical staining was conducted to detect the morphology of retinal neovascularization. H&E staining was performed to quantify retinal neovascularization. The qRT-PCR assay was applied to detect the expression levels of miR-29a and the AGT mRNA. Western blotting was used to detect the protein expressions of AGT, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), angiotensin (ANG) and angiotensin II (AngII). Results: Compared with the normal control group, miR-29a expression decreased, while the AGT mRNA expression and the protein expression levels of AGT, VEGF, HGF, ANG and AngII increased, and retinal vascular density and neovascularization also increased in the OIR group. In the OIR group, compared with the blank, empty plasmid, miR-29a inhibitors and miR-29a inhibitors + si-AGT groups, miR-29a expression increased, while the AGT mRNA expression and protein expression levels of AGT, VEGF, HGF, ANG and AngII decreased, and retinal vascular density and neovascularization also decreased in the miR-29a mimics, miR-29a mimics + si-AGT and si-AGT groups. Conclusion: MiR-29a could inhibit retinal neovascularization to prevent the development and progression of ROP by down-regulating AGT. PMID:28337307

  14. MET deregulation in breast cancer

    PubMed Central

    Landi, Lorenza

    2015-01-01

    Background Mesenchymal-epithelial transition (MET) is an oncogene encoding for a trans-membrane tyrosine kinase receptor activated by the hepatocyte growth factor (HGF). MET has a normal function in organ development during embryogenesis and in tissue homeostasis during adult life. Deregulation of HGF/MET signaling pathway is frequently observed in many cancer types, conferring invasive growth and tendency to progression. MET deregulation is due to gene amplification or increased copy number, gene mutation, receptor over-expression or ligand autocrine loops activation. These events lead to migration, invasion, proliferation, metastatic spread and neo-angiogenesis of cancer cells, suggesting that anti-HGF/MET agents may represent a potential antitumor strategy. In breast cancer (BC), preclinical and clinical data demonstrated the role of HGF/MET signalling pathway in carcinogenesis, disease progression and resistance features. Methods For this review article, all published data on HGF/MET in BC were collected and analyzed. Results Several evidences underline that, in early BC, MET over-expression has an independent negative prognostic significance, regardless of method used for evaluation and BC subtypes. Available data suggest that MET is a relevant target particularly in basal-like (BL) and in triple negative BC. Moreover, preclinical and retrospective data support the critical role of MET deregulation in the development of resistance to target-agents, such as anti-HER2 strategies. Conclusions MET is a promising new target in BC. Several anti-MET agents are under investigation and ongoing clinical trials will clarify its relevance in BC treatment. PMID:26366398

  15. Advanced Gas Turbine (AGT) powertrain system initial development report

    NASA Astrophysics Data System (ADS)

    1980-08-01

    The powertrain consists of a single shaft regenerated gas turbine engine utilizing ceramic hot section components, coupled to a slit differential gearbox with an available variable stator torque converter and an available Ford intergral overdrive four-speed automatic transmission. Predicted fuel economy using gasoline fuel over the combined federal driving cycle (CFDC) is 15.3 km/1, which represents a 59% improvement over the spark-ignition-powered baseline vehicle. Using DF2 fuel, CFDC mileage estimates are 17.43 km/1. Zero to 96.6 km/hr acceleration time is 11.9 seconds with a four-second accleration distance of 21.0 m. The ceramic radial turbine rotor is discussed along with the control system for the powertrain.

  16. Advanced Gas Turbine (AGT) powertrain system initial development report

    NASA Technical Reports Server (NTRS)

    1980-01-01

    The powertrain consists of a single shaft regenerated gas turbine engine utilizing ceramic hot section components, coupled to a slit differential gearbox with an available variable stator torque converter and an available Ford intergral overdrive four-speed automatic transmission. Predicted fuel economy using gasoline fuel over the combined federal driving cycle (CFDC) is 15.3 km/1, which represents a 59% improvement over the spark-ignition-powered baseline vehicle. Using DF2 fuel, CFDC mileage estimates are 17.43 km/1. Zero to 96.6 km/hr acceleration time is 11.9 seconds with a four-second accleration distance of 21.0 m. The ceramic radial turbine rotor is discussed along with the control system for the powertrain.

  17. Design firms shaken by utility deregulation

    SciTech Connect

    Korman, R.

    1994-04-11

    Deregulation of the US utility industry has wrought massive change in the engineering community. Power-plant design firms not only play with a livelier ball this spring, they`re playing an entirely new game.

  18. Three Agt1 transporters from brewer's yeasts exhibit different temperature dependencies for maltose transport over the range of brewery temperatures (0–20 °C).

    PubMed

    Vidgren, Virve; Viljanen, Kaarina; Mattinen, Laura; Rautio, Jari; Londesborough, John

    2014-06-01

    Zero-trans rates of maltose transport by brewer's yeasts exert strong control over fermentation rates and are strongly temperature-dependent over the temperature range (20–0 °C) of brewery fermentations. Three α-glucoside transporters, ScAgt1(A60) (a Saccharomyces cerevisiae version of Agt1 from an ale strain), ScAgt1-A548V (a variant of ScAgt1(A60) with a single amino acid change in a transmembrane domain), and SbAgt1 (a Saccharomyces (eu)bayanus version from a lager strain), were compared. When expressed in the same laboratory yeast, grown at 24 °C and assayed at 0, 10, and 20 °C, SbAgt1 had the lowest absolute maltose uptake activity at 20 °C but smallest temperature dependence, ScAgt1-A548V had the highest activity but greatest temperature dependence, and ScAgt1(A60) had intermediate properties. ScAgt1(A60) exhibited higher absolute rates and smaller temperature dependencies when expressed in laboratory rather than brewer's strains. Absolute rates closely reflected the amounts of GFP-tagged ScAgt1(A60) transporter in each host's plasma membrane. Growth at 15 °C instead of 24 °C decreased the absolute activities of strains expressing ScAgt1(A60) by two- to threefold. Evidently, the kinetic characteristics of at least ScAgt1(A60) depended on the nature of the host plasma membrane. However, no consistent correlation was observed between transport activities and fatty acid or ergosterol compositions.

  19. A polymorphism in AGT and AGTR1 gene is associated with lead-related high blood pressure.

    PubMed

    Kim, Hyung-Ki; Lee, Hwayoung; Kwon, Jun-Tack; Kim, Hak-Jae

    2015-12-01

    We investigated the association of polymorphisms in two renin-angiotensin system-related genes, expressed as angiotensinogen (AGT) and angiotensin II type 1 receptor (AGTR1), with blood lead levels and lead-related blood pressure in lead-exposed male workers in Korea. A cross-sectional study involving 808 lead-exposed male workers in Korea was conducted using a restriction fragment length polymorphism-based strategy to differentiate the various genotypes of polymorphisms in the AGT and AGTR1 genes. The association of clinical characteristics with genotypes as modifiers was estimated after adjustment for age, smoking status, drinking status, body mass index and job duration of each subject. Genotype and allele frequencies of the M235T polymorphism in AGT were associated with lead-related high blood pressure status. Moreover, blood lead levels were associated with allele frequencies of the AGT M235T polymorphism. These results suggested that the M/M genotype and M allele of AGT are risk factors for lead-related high blood pressure.

  20. Improved Fermentation Performance of a Lager Yeast after Repair of Its AGT1 Maltose and Maltotriose Transporter Genes▿ †

    PubMed Central

    Vidgren, Virve; Huuskonen, Anne; Virtanen, Hannele; Ruohonen, Laura; Londesborough, John

    2009-01-01

    The use of more concentrated, so-called high-gravity and very-high-gravity (VHG) brewer's worts for the manufacture of beer has economic and environmental advantages. However, many current strains of brewer's yeasts ferment VHG worts slowly and incompletely, leaving undesirably large amounts of maltose and especially maltotriose in the final beers. α-Glucosides are transported into Saccharomyces yeasts by several transporters, including Agt1, which is a good carrier of both maltose and maltotriose. The AGT1 genes of brewer's ale yeast strains encode functional transporters, but the AGT1 genes of the lager strains studied contain a premature stop codon and do not encode functional transporters. In the present work, one or more copies of the AGT1 gene of a lager strain were repaired with DNA sequence from an ale strain and put under the control of a constitutive promoter. Compared to the untransformed strain, the transformants with repaired AGT1 had higher maltose transport activity, especially after growth on glucose (which represses endogenous α-glucoside transporter genes) and higher ratios of maltotriose transport activity to maltose transport activity. They fermented VHG (24° Plato) wort faster and more completely, producing beers containing more ethanol and less residual maltose and maltotriose. The growth and sedimentation behaviors of the transformants were similar to those of the untransformed strain, as were the profiles of yeast-derived volatile aroma compounds in the beers. PMID:19181838

  1. Advanced Gas Turbine (AGT) powertrain system development for automotive applications report

    NASA Technical Reports Server (NTRS)

    1984-01-01

    This report describes progress and work performed during January through June 1984 to develop technology for an Advanced Gas Turbine (AGT) engine for automotive applications. Work performed during the first eight periods initiated design and analysis, ceramic development, component testing, and test bed evaluation. Project effort conducted under this contract is part of the DOE Gas Turbine Highway Vehicle System Program. This program is oriented at providing the United States automotive industry the high-risk long-range techology necessary to produce gas turbine engines for automobiles with reduced fuel consumption and reduced environmental impact. Technology resulting from this program is intended to reach the marketplace by the early 1990s.

  2. Deregulation-restructuring: Evidence for individual industries

    SciTech Connect

    Costello, K.W.; Graniere, R.J.

    1997-05-01

    Several studies have measured the effects of regulation on a particular industry. These studies range widely in sophistication, from simple observation (comparison) of pre-transformation and post-transformation actual industry performance to econometric analysis that attempt to separate the effects of deregulation from other factors in explaining changes in an industry`s performance. The major problem with observation studies is that they are unable to measure the effect of one particular event, such as deregulation, on an industry`s performance. For example, at the same time that the United Kingdom privatized its electric power industry, it also radically restructured the industry to encourage competition and instituted a price-cap mechanism to regulate the prices of transmission, distribution, and bundled retail services. Subsequent to these changes in 1991, real prices for most UK electricity customers have fallen. It is not certain however, which of these factors was most important or even contributed to the decline in price. In any event, one must be cautious in interpreting the results of studies that attempt to measure the effect of deregulation per se for a specific industry. This report highlights major outcomes for five industries undergoing deregulation or major regulatory and restructuring reforms. These include the natural gas, transportation, UK electric power, financial, and telecommunications industries. Particular attention was given to the historical development of events in the telecommunications industry.

  3. Deregulating electric utilities: issues and implications

    SciTech Connect

    Schmidt, R.H.

    1987-09-01

    This article presents an overview of the merits of continued utility regulation. To reach a better understanding of the issues involved, five related topics are discussed: the economic rationale for regulating utilities; traditional problems that have emerged with regulation in practice; recent theoretical and empirical evidence relating to the need for regulation; options for deregulation; and trends in construction of future power facilities in the present regulated environment. In general, evidence suggests that gains from regulation increasingly are negated by the disadvantages. Inefficiencies resulting from regulatory pricing have been accentuated by rapidly changing energy prices and inflation. Although some inefficiencies have been reduced by changes in rate proceedings, recent volatility in energy markets has increased the value of shifting to the more flexible pricing typically associated with deregulated markets. Furthermore, expected costs of deregulation may be less than initially envisioned. Gains from regulating the production of electricity have also been reduced by the apparent exhaustion of scale economies. There is increasing evidence that competitive forces can be used instead of regulation to produce low-cost electricity. Improvements in the technology of transmission have made spatial location of power generation less important, allowing producers at widely disparate locations to compete effectively in the same markets. The urgency of deregulation, however, is derived from concern about long-run supplies under regulation. Although present generating facilities are sufficient to meet demand over the next several years, additional capacity is likely to be necessary by the end of the century. 33 references, 4 figures, 2 tables.

  4. Role of ACE and AGT gene polymorphisms in genetic susceptibility to diabetes mellitus type 2 in a Brazilian sample.

    PubMed

    Wollinger, L M; Dal Bosco, S M; Rempe, C; Almeida, S E M; Berlese, D B; Castoldi, R P; Arndt, M E; Contini, V; Genro, J P

    2015-12-29

    The aim of the current study was to investigate the association between the InDel polymorphism in the angiotensin I-converting enzyme gene (ACE) and the rs699 polymorphism in the angiotensinogen gene (AGT) and diabetes mellitus type 2 (DM2) in a sample population from Southern Brazil. A case-control study was conducted with 228 patients with DM2 and 183 controls without DM2. The ACE InDel polymorphism was genotyped by polymerase chain reaction (PCR) with specific primers, followed by electrophoresis on 1.5% agarose gel. The AGT rs699 polymorphism was genotyped using a real-time PCR assay. No significant association between the ACE InDel polymorphism and DM2 was detected (P = 0.97). However, regarding the AGT rs699 polymorphism, DM2 patients had a significantly higher frequency of the AG genotype and lower frequency of the GG genotype when compared to the controls (P = 0.03). Our results suggest that there is an association between the AGT rs699 polymorphism and DM2 in a Brazilian sample.

  5. ATTAP/AGT101 - Year 2 progress in ceramic technology development

    NASA Technical Reports Server (NTRS)

    Kidwell, J. R.; Lindberg, L. J.; Morey, R. E.

    1990-01-01

    The progress made by the Advanced Turbine Technology Applications Project (ATTAP) is summarized, with emphasis on the following areas: ceramic materials assessment and characterization, ceramic impact damage assessment, ceramic combustor evaluation, turbine inlet particle separator development, impact-tolerant turbine designs, and net-shape ceramic component fabrications. In the evolutionary ceramics development in the Automotive Gas Turbine (AGT101) and ATTAP programs initial designs were conceived to reduce stresses by using well-established criteria: bodies of revolution were preferred over nonaxisymmetric geometries, sharp corners were avoided, the contact area between components was kept as large as possible, and small parts were preferred over large when feasible. Projects discussed include: initial ceramic component fabrication by ceramic suppliers in 1990, engine test to 1371 C in 1991, 100-hr test bed engine durability test in 1991, and 300-hr test bed engine durability in 1992.

  6. Utilities` ``obligation to serve`` under deregulation

    SciTech Connect

    Alexander, C.B.

    1997-02-01

    The utility no longer has protected status, and the traditional franchise concept is under attack. Exclusive rights once conveyed to the utilities are being denied and not just in the area of gas sales. Exclusive rights once conveyed to utilities will be denied in more areas. State by state, the utilities` franchise is being examined to see which, if any, of its provisions are necessary in a deregulated environment. Can the free market provide everything that`s been provided for many years under monopolistic arrangements? Some of the most critical and difficult of these provisions concern the obligation to serve, which utilities, in most states, have assumed as part of their franchise agreement. Regulators, courts, utilities, marketers and others are busy sorting through these issues, but resolution could take years. The paper discusses deregulation, universal service fee, representation without taxation, suppliers and marketer restrictions.

  7. Deregulation of Cell Signaling in Cancer

    PubMed Central

    Giancotti, Filippo G.

    2014-01-01

    Summary Oncogenic mutations disrupt the regulatory circuits that govern cell function, enabling tumor cells to undergo de-regulated mitogenesis, to resist to proapoptotic insults, and to invade through tissue boundaries. Cancer cell biology has played a crucial role in elucidating the signaling mechanisms by which oncogenic mutations sustain these malignant behaviors and thereby in identifying rational targets for cancer drugs. The efficacy of such targeted therapies illustrate the power of a reductionist approach to the study of cancer. PMID:24561200

  8. Air pollution effects due to deregulation of the electric industry

    NASA Astrophysics Data System (ADS)

    Davoodi, Khojasteh Riaz

    The Energy Policy Act of 1992 introduced the concept of open-access into the electric utility industry which allows privately-owned utilities to transmit power produced by non-utility generators and independent power producers (IPPs). In April 1996, the Federal Energy Regulatory Commission (FERC) laid down the final rules (Orders No. 888 & No. 889), which required utilities to open their transmission lines to any power producer and charge them no more than what they pay for the use of their own lines. These rules set the stage for the retail sale of electricity to industrial, commercial and residential utility customers; non-utility generators (Nugs); and power marketers. These statutory, regulatory and administrative changes create for the electric utility industry two different forces that contradict each other. The first is the concept of competition among utility companies; this places a greater emphasis on electric power generation cost control and affects generation/fuel mix selection and demand side management (DSM) activities. The second force, which is converse to the first, is that utilities are major contributors to the air pollution burden in the United States and environmental concerns are forcing them to reduce emissions of air pollutants by using more environmentally friendly fuels and implementing energy saving programs. This study evaluates the impact of deregulation within the investor owned electric utilities and how this deregulation effects air quality by investigating the trend in demand side management programs and generation/fuel mix. A survey was conducted of investor owned utilities and independent power producers. The results of the survey were analyzed by analysis of variance and regression analysis to determine the impact to Air Pollution. An air Quality Impact model was also developed in this study. This model consists of six modules: (1) demand side management and (2) consumption of coal, (3) gas, (4) renewable, (5) oil and (6

  9. Deregulation of Rho GTPases in cancer

    PubMed Central

    Porter, Andrew P.; Papaioannou, Alexandra; Malliri, Angeliki

    2016-01-01

    ABSTRACT In vitro and in vivo studies and evidence from human tumors have long implicated Rho GTPase signaling in the formation and dissemination of a range of cancers. Recently next generation sequencing has identified direct mutations of Rho GTPases in human cancers. Moreover, the effects of ablating genes encoding Rho GTPases and their regulators in mouse models, or through pharmacological inhibition, strongly suggests that targeting Rho GTPase signaling could constitute an effective treatment. In this review we will explore the various ways in which Rho signaling can be deregulated in human cancers. PMID:27104658

  10. Energy flow for electric power system deregulation

    NASA Astrophysics Data System (ADS)

    Lin, Chia-Hung

    Over the past few years, the electric power utility industry in North America and other countries has experienced a strong drive towards deregulation. People have considered the necessity of deregulation of electric utilities for higher energy efficiency and energy saving. The vertically integrated monopolistic industry is being transferred into a horizontally integrated competitive structure in some countries. Wheeling charges are a current high priority problem throughout the power industry, for independent power producers, as well as regulators. Nevertheless the present transmission pricing mechanism fails to be adjusted by a customer loading condition. Customer loading is dynamic, but the present wheeling charge method is fixed, not real-time. A real-time wheeling charge method is developed in this dissertation. This dissertation introduces a concept of a power flow network which can be used for the calculation of power contribution factors in a network. The contribution factor is defined as the ratio of the power contributed by a particular source to a line flow or bus load to the total output of the source. Generation, transmission, and distribution companies can employ contribution factors for the calculation of energy cost, wheeling charges, and loss compensation. Based on the concept of contribution factors, a proposed loss allocation method is developed in this dissertation. Besides, counterflow condition will be given a credit in the proposed loss allocation method. A simple 22-bus example was used for evaluating the contribution factors, proposed wheeling charge method, and loss allocation method.

  11. The AGT Gene M235T Polymorphism and Response of Power-Related Variables to Aerobic Training

    PubMed Central

    Aleksandra, Zarębska; Zbigniew, Jastrzębski; Waldemar, Moska; Agata, Leońska-Duniec; Mariusz, Kaczmarczyk; Marek, Sawczuk; Agnieszka, Maciejewska-Skrendo; Piotr, Żmijewski; Krzysztof, Ficek; Grzegorz, Trybek; Ewelina, Lulińska-Kuklik; Semenova, Ekaterina A.; Ahmetov, Ildus I.; Paweł, Cięszczyk

    2016-01-01

    The C allele of the M235T (rs699) polymorphism of the AGT gene correlates with higher levels of angiotensin II and has been associated with power and strength sport performance. The aim of the study was to investigate whether or not selected power-related variables and their response to a 12-week program of aerobic dance training are modulated by the AGT M235T genotype in healthy participants. Two hundred and one Polish Caucasian women aged 21 ± 1 years met the inclusion criteria and were included in the study. All women completed a 12-week program of low and high impact aerobics. Wingate peak power and total work capacity, 5 m, 10 m, and 30 m running times and jump height and jump power were determined before and after the training programme. All power-related variables improved significantly in response to aerobic dance training. We found a significant association between the M235T polymorphism and jump-based variables (squat jump (SJ) height, p = 0.005; SJ power, p = 0.015; countermovement jump height, p = 0.025; average of 10 countermovement jumps with arm swing (ACMJ) height, p = 0.001; ACMJ power, p = 0.035). Specifically, greater improvements were observed in the C allele carriers in comparison with TT homozygotes. In conclusion, aerobic dance, one of the most commonly practiced adult fitness activities in the world, provides sufficient training stimuli for augmenting the explosive strength necessary to increase vertical jump performance. The AGT gene M235T polymorphism seems to be not only a candidate gene variant for power/strength related phenotypes, but also a genetic marker for predicting response to training. Key points Aerobic dance provides sufficient training stimuli for the improvement of explosive power. The AGT gene M235T polymorphism is associated with individual variation in the change of power-related phenotypes in response to aerobic dance training. The C allele carriers of the AGT gene M235T polymorphism show greater improvements of jump

  12. Federal Acquisition Regulation (FAR) Revisions for Telecommunications

    DTIC Science & Technology

    1987-04-01

    have depended on monopolies to provide telecommun for over 75 years. In light of the Federal Commu Commission (FCC) deregulation of the telecommunic...effects deregulation and divestiture have had on of telecommunication services and adjust its acqu and procedures to assure continued commercial...34). In addition to this simplified "pricing" approach to tariffed telephone services (i.e., acceptance of tariffed prices), the ASPR established

  13. Detection of Deregulated Modules Using Deregulatory Linked Path

    PubMed Central

    Hu, Yuxuan; Gao, Lin; Shi, Kai; Chiu, David K. Y.

    2013-01-01

    The identification of deregulated modules (such as induced by oncogenes) is a crucial step for exploring the pathogenic process of complex diseases. Most of the existing methods focus on deregulation of genes rather than the links of the path among them. In this study, we emphasize on the detection of deregulated links, and develop a novel and effective regulatory path-based approach in finding deregulated modules. Observing that a regulatory pathway between two genes might involve in multiple rather than a single path, we identify condition-specific core regulatory path (CCRP) to detect the significant deregulation of regulatory links. Using time-series gene expression, we define the regulatory strength within each gene pair based on statistical dependence analysis. The CCRPs in regulatory networks can then be identified using the shortest path algorithm. Finally, we derive the deregulated modules by integrating the differential edges (as deregulated links) of the CCRPs between the case and the control group. To demonstrate the effectiveness of our approach, we apply the method to expression data associated with different states of Human Epidermal Growth Factor Receptor 2 (HER2). The experimental results show that the genes as well as the links in the deregulated modules are significantly enriched in multiple KEGG pathways and GO biological processes, most of which can be validated to suffer from impact of this oncogene based on previous studies. Additionally, we find the regulatory mechanism associated with the crucial gene SNAI1 significantly deregulated resulting from the activation of HER2. Hence, our method provides not only a strategy for detecting the deregulated links in regulatory networks, but also a way to identify concerning deregulated modules, thus contributing to the target selection of edgetic drugs. PMID:23894653

  14. Novel regulation of Skp1 by the Dictyostelium AgtA α-galactosyltransferase involves the Skp1-binding activity of its WD40 repeat domain.

    PubMed

    Schafer, Christopher M; Sheikh, M Osman; Zhang, Dongmei; West, Christopher M

    2014-03-28

    The role of Skp1 as an adaptor protein that links Cullin-1 to F-box proteins in E3 Skp1/Cullin-1/F-box protein (SCF) ubiquitin ligases is well characterized. In the social amoeba Dictyostelium and probably many other unicellular eukaryotes, Skp1 is modified by a pentasaccharide attached to a hydroxyproline near its C terminus. This modification is important for oxygen-sensing during Dictyostelium development and is mediated by a HIF-α type prolyl 4-hydroxylase and five sequentially acting cytoplasmic glycosyltransferase activities. Gene disruption studies show that AgtA, the enzyme responsible for addition of the final two galactose residues, in α-linkages to the Skp1 core trisaccharide, is unexpectedly critical for oxygen-dependent terminal development. AgtA possesses a WD40 repeat domain C-terminal to its single catalytic domain and, by use of domain deletions, binding studies, and enzyme assays, we find that the WD40 repeats confer a salt-sensitive second-site binding interaction with Skp1 that mediates novel catalytic activation in addition to simple substrate recognition. In addition, AgtA binds similarly well to precursor isoforms of Skp1 by a salt-sensitive mechanism that competes with binding to an F-box protein and recognition by early modification enzymes, and the effect of binding is diminished when AgtA modifies Skp1. Genetic studies show that loss of AgtA is more severe when an earlier glycosylation step is blocked, and overexpressed AgtA is deleterious if catalytically inactivated. Together, the findings suggest that AgtA mediates non-enzymatic control of unmodified and substrate precursor forms of Skp1 by a binding mechanism that is normally relieved by switch-like activation of its glycosylation function.

  15. Telecommunications Policy Research Conference. Regulation, Deregulation & Competition Section. Papers.

    ERIC Educational Resources Information Center

    Telecommunications Policy Research Conference, Inc., Washington, DC.

    Three papers discuss aspects of telecommunications regulation in a deregulated environment. The first paper, "Implementing Telephone Deregulation: The Political Economy of State Regulation in the Post-Divestiture Era" (Paul E. Teske), analyzed the variation in state regulation of local telephone operating companies using regression…

  16. Television News and Broadcast Deregulation in New Zealand.

    ERIC Educational Resources Information Center

    Comrie, Margie

    1999-01-01

    Contributes to scholarship on broadcast deregulation and news-source diversity, tracing sourcing patterns on prime-time news across a 12-year period encompassing the deregulation of broadcasting in New Zealand. Finds that increasing commercialism resulted in shorter sound bites; reduced use of official cited sources; and a greater use of nonelite…

  17. Regulation and deregulation of natural gas in the US: 1938-1985

    SciTech Connect

    Merrill, Peter R.

    1980-06-01

    Public policy towards natural gas has swung first towards, and then away from regulation in this century. In 1906, the Congress specifically excluded natural gas from the jurisdiction of the Interstate Commerce Commission. Three decades later, a New Deal Congress passed the Natural Gas Act of 1938 bringing pipelines under the control of the Federal Power Commission (FDC). Forty years thereafter, the Congress passed a phased decontrol bill, the Natural Gas Policy Act (NGPA) of 1978, as part of the Carter Administration's National Energy Plan. Recently, the Congress has backed off from New Deal legislation in other markets - notably aviation and trucking. In this study, the rise and fall of economic regulation in the natural gas industry are examined to understand: (1) why public policy has followed a pendulum's path, and (2) the economic consequences of regulation and deregulation. The main part of the analysis is directed toward the Natural Gas Policy Act of 1978. Widely viewed as a deregulation measure, the author finds that the Act is more restrictive and burdensome than the pricing policies it superceded. The path toward deregulation in natural gas and perhaps other markets is not as direct or simple as might be expected.

  18. Deregulation and Nuclear Training: Cost Effective Alternatives

    SciTech Connect

    Richard P. Coe; Patricia A. Lake

    2000-11-12

    Training is crucial to the success of any organization. It is also expensive, with some estimates exceeding $50 billion annually spent on training by U.S. corporations. Nuclear training, like that of many other highly technical organizations, is both crucial and costly. It is unlikely that the amount of training can be significantly reduced. If anything, current trends indicate that training needs will probably increase as the industry and workforce ages and changes. With the advent of energy deregulation in the United States, greater pressures will surface to make the costs of energy more cost-competitive. This in turn will drive businesses to more closely examine existing costs and find ways to do things in a more cost-effective way. The commercial nuclear industry will be no exception, and nuclear training will be equally affected. It is time for nuclear training and indeed the entire nuclear industry to begin using more aggressive techniques to reduce costs. This includes the need for nuclear training to find alternatives to traditional methods for the delivery of cost-effective high-quality training that meets regulatory requirements and produces well-qualified personnel capable of working in an efficient and safe manner. Computer-based and/or Web-based training are leading emerging technologies.

  19. Efficiency in the United States electric industry: Transaction costs, deregulation, and governance structures

    NASA Astrophysics Data System (ADS)

    Peterson, Carl

    Transaction costs economics (TCE) posits that firms have an incentive to bypass the market mechanisms in situations where the cost of using the market is prohibitive. Vertical integration, among other governance mechanisms, can be used to minimize the transactions costs associated with the market mechanism. The study analyses different governance mechanisms, which range from complete vertical integration to the use of market mechanisms, for firms in the US electric sector. This sector has undergone tremendous change in the past decade including the introduction of retail competition in some jurisdictions. As a result of the push toward deregulation of the industry, vertically integration, while still significant in the sector, has steadily been replaced by alternative governance structures. Using a sample of 136 investor-owned electric utilities that reported data the US Federal Energy Regulatory Commission between 1996 and 2002, this study estimates firm level efficiency using Data Envelopment Analysis (DEA) and relates these estimates to governance structure and public policies. The analysis finds that vertical integration is positively related to firm efficiency, although in a non-linear fashion suggesting that hybrid governance structures tend to be associated with lower efficiency scores. In addition, while some evidence is found for negative short-term effects on firm efficiency from the choice to deregulate, this result is sensitive to DEA model choice. Further, competition in retail markets is found to be positively related to firm level efficiency, but the retreat from deregulation, which occurred after 2000, is negatively associated with firm-level efficiency. These results are important in the ongoing academic and public policy debates concerning deregulation of the electric section and indicate that vertical economies remain in the industry, but that competition has provided incentives for improving firm level efficiency.

  20. Combinatorial Study of Ag-Te Thin Films and Their Application as Cation Supply Layer in CBRAM Cells.

    PubMed

    Devulder, Wouter; Opsomer, Karl; Meersschaut, Johan; Deduytsche, Davy; Jurczak, Malgorzata; Goux, Ludovic; Detavernier, Christophe

    2015-05-11

    In this work, we investigate binary Ag-Te thin films and their functionality as a cation supply layer in conductive bridge random access memory devices. A combinatorial sputter deposition technique is used to deposit a graded Ag(x)Te(1-x) (0 < x < 1) layer with varying composition as a function of the position on the substrate. The crystallinity, surface morphology, and material stability under thermal treatment as a function of the composition of the material are investigated. From this screening, a narrow composition range between 33 and 38 at% Te is selected which shows a good morphology and a high melting temperature. Functionality of a single Ag(2-δ)Te composition as cation supply layer in CBRAM with dedicated Al2O3 switching layer is then investigated by implementing it in 580 μm diameter dot Pt/Ag(2-δ)Te/Al2O3/Si cells. Switching properties are investigated and compared to cells with a pure Ag cation supply layer. An improved cycling behavior is observed when Te is added compared to pure Ag, which we relate to the ionic conducting properties of Ag2Te and the preferred formation of Ag-Te phases.

  1. Mutagenicity associated with O6-methylguanine-DNA damage and mechanism of nucleotide flipping by AGT during repair

    NASA Astrophysics Data System (ADS)

    Jena, N. R.; Bansal, Manju

    2011-08-01

    Methylated guanine damage at O6 position (i.e. O6MG) is dangerous due to its mutagenic and carcinogenic character that often gives rise to G:C-A:T mutation. However, the reason for this mutagenicity is not known precisely and has been a matter of controversy. Further, although it is known that O6-alkylguanine-DNA alkyltransferase (AGT) repairs O6MG paired with cytosine in DNA, the complete mechanism of target recognition and repair is not known completely. All these aspects of DNA damage and repair have been addressed here by employing high level density functional theory in gas phase and aqueous medium. It is found that the actual cause of O6MG mediated mutation may arise due to the fact that DNA polymerases incorporate thymine opposite to O6MG, misreading the resulting O6MG:T complex as an A:T base pair due to their analogous binding energies and structural alignments. It is further revealed that AGT mediated nucleotide flipping occurs in two successive steps. The intercalation of the finger residue Arg128 into the DNA double helix and its interaction with the O6MG:C base pair followed by rotation of the O6MG nucleotide are found to be crucial for the damage recognition and nucleotide flipping.

  2. Deregulation of DUX4 and ERG in acute lymphoblastic leukemia.

    PubMed

    Zhang, Jinghui; McCastlain, Kelly; Yoshihara, Hiroki; Xu, Beisi; Chang, Yunchao; Churchman, Michelle L; Wu, Gang; Li, Yongjin; Wei, Lei; Iacobucci, Ilaria; Liu, Yu; Qu, Chunxu; Wen, Ji; Edmonson, Michael; Payne-Turner, Debbie; Kaufmann, Kerstin B; Takayanagi, Shin-Ichiro; Wienholds, Erno; Waanders, Esmé; Ntziachristos, Panagiotis; Bakogianni, Sofia; Wang, Jingjing; Aifantis, Iannis; Roberts, Kathryn G; Ma, Jing; Song, Guangchun; Easton, John; Mulder, Heather L; Chen, Xiang; Newman, Scott; Ma, Xiaotu; Rusch, Michael; Gupta, Pankaj; Boggs, Kristy; Vadodaria, Bhavin; Dalton, James; Liu, Yanling; Valentine, Marcus L; Ding, Li; Lu, Charles; Fulton, Robert S; Fulton, Lucinda; Tabib, Yashodhan; Ochoa, Kerri; Devidas, Meenakshi; Pei, Deqing; Cheng, Cheng; Yang, Jun; Evans, William E; Relling, Mary V; Pui, Ching-Hon; Jeha, Sima; Harvey, Richard C; Chen, I-Ming L; Willman, Cheryl L; Marcucci, Guido; Bloomfield, Clara D; Kohlschmidt, Jessica; Mrózek, Krzysztof; Paietta, Elisabeth; Tallman, Martin S; Stock, Wendy; Foster, Matthew C; Racevskis, Janis; Rowe, Jacob M; Luger, Selina; Kornblau, Steven M; Shurtleff, Sheila A; Raimondi, Susana C; Mardis, Elaine R; Wilson, Richard K; Dick, John E; Hunger, Stephen P; Loh, Mignon L; Downing, James R; Mullighan, Charles G

    2016-12-01

    Chromosomal rearrangements deregulating hematopoietic transcription factors are common in acute lymphoblastic leukemia (ALL). Here we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG is a hallmark of a subtype of B-progenitor ALL that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression was present in all cases and was accompanied by transcriptional deregulation of ERG, expression of a novel ERG isoform, ERGalt, and frequent ERG deletion. ERGalt uses a non-canonical first exon whose transcription was initiated by DUX4 binding. ERGalt retains the DNA-binding and transactivation domains of ERG, but it inhibits wild-type ERG transcriptional activity and is transforming. These results illustrate a unique paradigm of transcription factor deregulation in leukemia in which DUX4 deregulation results in loss of function of ERG, either by deletion or induced expression of an isoform that is a dominant-negative inhibitor of wild-type ERG function.

  3. AgtA, the Dicarboxylic Amino Acid Transporter of Aspergillus nidulans, Is Concertedly Down-Regulated by Exquisite Sensitivity to Nitrogen Metabolite Repression and Ammonium-Elicited Endocytosis▿ †

    PubMed Central

    Apostolaki, Angeliki; Erpapazoglou, Zoi; Harispe, Laura; Billini, Maria; Kafasla, Panagiota; Kizis, Dimosthenis; Peñalva, Miguel Angel; Scazzocchio, Claudio; Sophianopoulou, Vicky

    2009-01-01

    We identified agtA, a gene that encodes the specific dicarboxylic amino acid transporter of Aspergillus nidulans. The deletion of the gene resulted in loss of utilization of aspartate as a nitrogen source and of aspartate uptake, while not completely abolishing glutamate utilization. Kinetic constants showed that AgtA is a high-affinity dicarboxylic amino acid transporter and are in agreement with those determined for a cognate transporter activity identified previously. The gene is extremely sensitive to nitrogen metabolite repression, depends on AreA for its expression, and is seemingly independent from specific induction. We showed that the localization of AgtA in the plasma membrane necessitates the ShrA protein and that an active process elicited by ammonium results in internalization and targeting of AgtA to the vacuole, followed by degradation. Thus, nitrogen metabolite repression and ammonium-promoted vacuolar degradation act in concert to downregulate dicarboxylic amino acid transport activity. PMID:19168757

  4. Electric Restructuring and Utilities Deregulation: A Facility Manager's Guide.

    ERIC Educational Resources Information Center

    Glazner, Steve, Ed.

    This volume presents 12 papers offering guidelines to higher education institutions on planning for the deregulation of the electric power industry. Following an introduction (by Dorsey D. Jacobs), the papers are organized into three parts which address: the changing market, identifying opportunities and challenges, and taking advantage of…

  5. Deregulation of University Education in Nigeria: Problems and Prospects

    ERIC Educational Resources Information Center

    Adeogun, A. A.; Subair, S. T.; Osifila, G. I.

    2009-01-01

    This paper focuses on the deregulation of university education in Nigeria, its problems and prospects. The paper commences with the recognition given to education all over the world, especially higher education. Nigeria as a country gives much credence to higher education as the means for social and economic mobility, social transformation, and as…

  6. U.S. Broadcast Deregulation: A Case of Dubious Evidence.

    ERIC Educational Resources Information Center

    Levin, Harry J.

    1986-01-01

    Reviews the empirical evidence cited by the FCC in favor of increasing the allowable number of radio and TV stations owned by one group. Argues FCC was biased in favor of deregulation despite weighty evidence indicating continued need for regulation. (MS)

  7. Evaluating an Ice-Storage System in a Deregulated Environment.

    ERIC Educational Resources Information Center

    Staniewicz, Theodore J.; Watson, Joseph J.

    2001-01-01

    Examines the difficulties the electric industry's deregulation created for St. Joseph's University's (Philadelphia) development of a thermal ice-storage system as part of its HVAC design and the school's solution. A monthly equipment summary sheet with year-to-date figures is provided. (GR)

  8. Teacher Education Policy in Canada: Beyond Professionalization and Deregulation

    ERIC Educational Resources Information Center

    Walker, Judith; von Bergmann, HsingChi

    2013-01-01

    This paper empirically investigates Grimmett's (2008, 2009) thesis that recent Canadian teacher education policy is best characterized by dual forces of deregulation and professionalization resulting from a neoliberal policy environment. Specifically, we examine teacher education governance, policy reform, and political context from 2000 to 2010,…

  9. 75 FR 68321 - Forage Genetics International; Supplemental Request for Partial Deregulation of Roundup Ready...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-05

    ... Animal and Plant Health Inspection Service Forage Genetics International; Supplemental Request for... ``partial deregulation'' from Forage Genetics International for the planting, harvesting, and movement... submitted to the Agency from Forage Genetics International requesting a ``partial deregulation.''...

  10. Chile: pioneer in deregulation of the electric power sector

    SciTech Connect

    Rudnick, H. )

    1994-06-01

    This article examines the deregulation of the electric power sector in Chile. Chile was the leader in Latin America in the restructuring of the electric power sector, and its case merits particular analysis. Although a small system (70% of installed capacity is hydroelectric with 2,800 MW maximum demand in 1993), its development has been observed with interest by many institutions, particularly by the World Bank and most recently by other Latin American countries, and several countries have followed its steps. The Chilean 1982 electricity law was a worldwide pioneer in deregulating the electric power sector to create market conditions where generators compete to provide electrical energy to large consumers, sharing a transmission system open to all and paying fees for that system. The law formalized what had taken place in the country since 1978, several years before market approaches were formulated in the US and implemented in the United Kingdom.

  11. Generation capacity expansion planning in deregulated electricity markets

    NASA Astrophysics Data System (ADS)

    Sharma, Deepak

    With increasing demand of electric power in the context of deregulated electricity markets, a good strategic planning for the growth of the power system is critical for our tomorrow. There is a need to build new resources in the form of generation plants and transmission lines while considering the effects of these new resources on power system operations, market economics and the long-term dynamics of the economy. In deregulation, the exercise of generation planning has undergone a paradigm shift. The first stage of generation planning is now undertaken by the individual investors. These investors see investments in generation capacity as an increasing business opportunity because of the increasing market prices. Therefore, the main objective of such a planning exercise, carried out by individual investors, is typically that of long-term profit maximization. This thesis presents some modeling frameworks for generation capacity expansion planning applicable to independent investor firms in the context of power industry deregulation. These modeling frameworks include various technical and financing issues within the process of power system planning. The proposed modeling frameworks consider the long-term decision making process of investor firms, the discrete nature of generation capacity addition and incorporates transmission network modeling. Studies have been carried out to examine the impact of the optimal investment plans on transmission network loadings in the long-run by integrating the generation capacity expansion planning framework within a modified IEEE 30-bus transmission system network. The work assesses the importance of arriving at an optimal IRR at which the firm's profit maximization objective attains an extremum value. The mathematical model is further improved to incorporate binary variables while considering discrete unit sizes, and subsequently to include the detailed transmission network representation. The proposed models are novel in the

  12. Managing an evolution: Deregulation of the electric utility industry

    SciTech Connect

    Skinner, S.K.

    1994-12-31

    The author discusses the emerging competitive situation in the electric power industry as deregulation of electric utilities looms on the horizon. The paper supports this change, and the competition it will bring, but urges caution as changes are instituted, and the regulatory bodies decide how and how much to free, and at what rates. The reason for his urge for caution comes from historical experience of other industries, which were smaller and had less direct impact on every American.

  13. Recurrently deregulated lncRNAs in hepatocellular carcinoma

    PubMed Central

    Yang, Yang; Chen, Lei; Gu, Jin; Zhang, Hanshuo; Yuan, Jiapei; Lian, Qiuyu; Lv, Guishuai; Wang, Siqi; Wu, Yang; Yang, Yu-Cheng T.; Wang, Dongfang; Liu, Yang; Tang, Jing; Luo, Guijuan; Li, Yang; Hu, Long; Sun, Xinbao; Wang, Dong; Guo, Mingzhou; Xi, Qiaoran; Xi, Jianzhong; Wang, Hongyang; Zhang, Michael Q.; Lu, Zhi John

    2017-01-01

    Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples' RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data. Matched array data from the 60 samples show that copy number variations (CNVs) and alterations in DNA methylation contribute to the observed recurrent deregulation of 235 lncRNAs. Many recurrently deregulated lncRNAs are enriched in co-expressed clusters of genes related to cell adhesion, immune response and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1, were further validated using RNAi-based loss-of-function assays. Thus, we provide a valuable resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis. PMID:28194035

  14. Deregulation strategies for local governments and the role/opportunities for energy efficiency services in the utility industry deregulation

    SciTech Connect

    Tseng, P.C.

    1998-07-01

    As the future shape of the electric utility industry continues to unfold and as retail competition becomes a reality, local governments are faced with balancing the need for: (1) economic development; (2) and to avoid the potential impact of cost-shifting among residents and businesses, while ensuring reliable and universal energy services. Furthermore, local governments need to find ways to recoup potential loss of franchise and tax revenues, to ensure fair and adequate energy-efficiency programs, and to continue other social programs for low income families. This paper will address two important issues every local government in the US are facing: (1) the development of viable deregulation strategies before, during and after the promulgation of utility deregulation; (2) opportunities for energy efficiency services in the competitive markets to serve local governments, which typically constitutes the largest market segment in utility's service territory. This paper presents issues and challenges common to all local governments. It documents strategies that several local governments are utilizing to embrace the coming electric utility restructuring and competition challenge to the benefits of their respective communities. This paper presents the results on deregulation work by the City of Portland, Oregon, Barnstable County, Massachusetts, and Montgomery County, Maryland. The research by these local governments was sponsored by the Urban Consortium Energy Task Force and Public Technology, Inc.

  15. Power systems locational marginal pricing in deregulated markets

    NASA Astrophysics Data System (ADS)

    Wang, Hui-Fung Francis

    Since the beginning of the 1990s, the electricity business is transforming from a vertical integrating business to a competitive market operations. The generation, transmission, distribution subsystem of an electricity utility are operated independently as Genco (generation subsystem), Transco (transmission subsystem), and Distco (distribution subsystem). This trend promotes more economical inter- and intra regional transactions to be made by the participating companies and the users of electricity to achieve the intended objectives of deregulation. There are various types of electricity markets that are implemented in the North America in the past few years. However, transmission congestion management becomes a key issue in the electricity market design as more bilateral transactions are traded across long distances competing for scarce transmission resources. It directly alters the traditional concept of energy pricing and impacts the bottom line, revenue and cost of electricity, of both suppliers and buyers. In this research, transmission congestion problem in a deregulated market environment is elucidated by implementing by the Locational Marginal Pricing (LMP) method. With a comprehensive understanding of the LMP method, new mathematical tools will aid electric utilities in exploring new business opportunities are developed and presented in this dissertation. The dissertation focuses on the development of concept of (LMP) forecasting and its implication to the market participants in deregulated market. Specifically, we explore methods of developing fast LMP calculation techniques that are differ from existing LMPs. We also explore and document the usefulness of the proposed LMP in determining electricity pricing of a large scale power system. The developed mathematical tools use of well-known optimization techniques such as linear programming that are support by several flow charts. The fast and practical security constrained unit commitment methods are the

  16. Will deregulating natural gas increase its price to consumers

    SciTech Connect

    Brown, S.P.A.

    1983-07-01

    Although it is likely that deregulation will increase the price consumers must pay for natural gas, this increase will occur only if the supply of gas contracts. Decontrol will result in higher wellhead prices and increased production for some categories of gas and lower wellhead prices and decreased production for others. The net effect on the supply of gas and, hence, on the consumer price of gas is not completely clear. However, an analysis of the limited data available suggests that decontrol will probably yield a reduced supply and a higher consumer price. 6 references, 2 figures, 4 tables.

  17. Cell cycle deregulation by methyl isocyanate: Implications in liver carcinogenesis.

    PubMed

    Panwar, Hariom; Raghuram, Gorantla V; Jain, Deepika; Ahirwar, Alok K; Khan, Saba; Jain, Subodh K; Pathak, Neelam; Banerjee, Smita; Maudar, Kewal K; Mishra, Pradyumna K

    2014-03-01

    Liver is often exposed to plethora of chemical toxins. Owing to its profound physiological role and central function in metabolism and homeostasis, pertinent succession of cell cycle in liver epithelial cells is of prime importance to maintain cellular proliferation. Although recent evidence has displayed a strong association between exposures to methyl isocyanate (MIC), one of the most toxic isocyanates, and neoplastic transformation, molecular characterization of the longitudinal effects of MIC on cell cycle regulation has never been performed. Here, we sequentially delineated the status of different proteins arbitrating the deregulation of cell cycle in liver epithelial cells treated with MIC. Our data reaffirms the oncogenic capability of MIC with elevated DNA damage response proteins pATM and γ-H2AX, deregulation of DNA damage check point genes CHK1 and CHK2, altered expression of p53 and p21 proteins involved in cell cycle arrest with perturbation in GADD-45 expression in the treated cells. Further, alterations in cyclin A, cyclin E, CDK2 levels along with overexpression of mitotic spindle checkpoints proteins Aurora A/B, centrosomal pericentrin protein, chromosomal aberrations, and loss of Pot1a was observed. Thus, MIC impacts key proteins involved in cell cycle regulation to trigger genomic instability as a possible mechanism of developmental basis of liver carcinogenesis.

  18. Economic deregulation and transport safety: a synthesis of evidence from evaluation studies.

    PubMed

    Elvik, Rune

    2006-07-01

    This paper presents a synthesis of evidence from studies that have evaluated the impacts of economic deregulation on transport safety. Most of these studies refer to aviation or road transport. Very few studies deal with deregulation of rail transport. There are no studies of maritime transport, which has never been regulated the same way as other modes of transport. The review includes studies that have attempted to quantify the impacts of transport deregulation on transport safety. Each study contains one or more estimates of the effect on transport safety of deregulation. Summary estimates of effect have been derived from the individual estimates of effect by means of meta-analysis. Airline deregulation, which has only been evaluated in the United States, does not appear to influence the safety of air travel. Deregulation of road transport has been evaluated in several countries. The summary estimate of effect indicates that no statistically significant changes in road safety have occurred as a result of deregulation. Deregulation of rail transport has only been evaluated in Great Britain and the United States. The experience so far suggests that deregulation of railways is associated with improved rail safety. This association does, however, not necessarily imply a causal relationship.

  19. The effects of deregulation on rural electric distribution cooperatives: An empirical analysis

    NASA Astrophysics Data System (ADS)

    Greer, Monica Lynne

    In 1996, the Federal Energy Regulatory Commission ("FERC") issued Orders 888 and 889, which were designed to promote competition in wholesale markets for electricity. While these Orders were predominantly meant to apply to vertically integrated investor-owned utilities ("IOUs"), FERC recently issued a Notice of Proposed Rulemaking that indicates its intent to make all transmission-owning entities, including those of cooperatively-owned utilities and the federal power administrations subject to FERC jurisdiction. Cooperatively owned utilities ("coops"), the focus of this paper, are organized as either generation and transmission ("G&T") or distribution only. And, although there are typically long-term contracts between the G&T and the distribution coops (thus rendering them quasi-vertically-integrated), they are very different from their investor-owned counterparts. It is because of these differences that the economic viability of these entities is being questioned in a deregulated environment. This dissertation examines the ability of coops to continue operating in their present form in a restructured electricity market. More specifically, using 1996 data for 831 distribution coops I estimate both quadratic and translogarithmic cost specifications so as to ascertain whether these firms are operating in such a fashion as to minimize costs. I find evidence that they are not. When delivered power is modeled as a single-output translogarithmic cost equation, I find that the majority of firms in the sample were operating in the increasing returns to scale portion of the average cost curve in 1996. This result reveals that coops delivered far less electricity to all customer classes than was necessary to attain the minimum efficient scale. And, upon estimating a multiple-output quadratic cost function, I find that there are ray economies, product specific returns to scale, and economies of scope in the distribution of electricity to the various customer classes that are

  20. Advanced Gas Turbine (AGT)

    NASA Technical Reports Server (NTRS)

    1983-01-01

    The development and progress of the Advanced Gas Turbine engine program is examined. An analysis of the role of ceramics in the design and major engine components is included. Projected fuel economy, emissions and performance standards, and versatility in fuel use are also discussed.

  1. Advanced GPS Technologies (AGT)

    DTIC Science & Technology

    2015-05-01

    AND ADDRESS(ES) Air Force Research Laboratory,Space Vehicles Directorate,3550 Aberdeen Avenue SE , Kirtland AFB,NM,87117 8. PERFORMING ORGANIZATION...Inform Partnership Council about AFRL technology investments to improve affordability and performance of the GPS Space Segment Summary • Working in...development Exploring/opening paths to the future! Distribution A 2 \\.J ••• • AFRL Investments Supporting GPS Space Segment • AFRL is investigating

  2. Do cost-sharing and entry deregulation curb pharmaceutical innovation?

    PubMed

    Grossmann, Volker

    2013-09-01

    This paper examines the role of both cost-sharing schemes in health insurance systems and the regulation of entry into the pharmaceutical sector for pharmaceutical R&D expenditure and drug prices. The analysis suggests that both an increase in the coinsurance rate and stricter price regulations adversely affect R&D spending in the pharmaceutical sector. In contrast, entry deregulation may lead to higher R&D spending of pharmaceutical companies. The relationship between R&D spending per firm and the number of firms may be hump-shaped. In this case, the number of rivals which maximizes R&D expenditure per firm is decreasing in the coinsurance rate and increasing in labor productivity.

  3. Regional copy number-independent deregulation of transcription in cancer.

    PubMed

    Stransky, Nicolas; Vallot, Céline; Reyal, Fabien; Bernard-Pierrot, Isabelle; de Medina, Sixtina Gil Diez; Segraves, Rick; de Rycke, Yann; Elvin, Paul; Cassidy, Andrew; Spraggon, Carolyn; Graham, Alexander; Southgate, Jennifer; Asselain, Bernard; Allory, Yves; Abbou, Claude C; Albertson, Donna G; Thiery, Jean Paul; Chopin, Dominique K; Pinkel, Daniel; Radvanyi, François

    2006-12-01

    Genetic and epigenetic alterations have been identified that lead to transcriptional deregulation in cancers. Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing. Various techniques are available for identifying regional genetic alterations, but no large-scale analysis has yet been carried out to obtain an overview of regional epigenetic alterations. We carried out an exhaustive search for regions susceptible to such mechanisms using a combination of transcriptome correlation map analysis and array CGH data for a series of bladder carcinomas. We validated one candidate region experimentally, demonstrating histone methylation leading to the loss of expression of neighboring genes without DNA methylation.

  4. Game-theoretic equilibrium analysis applications to deregulated electricity markets

    NASA Astrophysics Data System (ADS)

    Joung, Manho

    This dissertation examines game-theoretic equilibrium analysis applications to deregulated electricity markets. In particular, three specific applications are discussed: analyzing the competitive effects of ownership of financial transmission rights, developing a dynamic game model considering the ramp rate constraints of generators, and analyzing strategic behavior in electricity capacity markets. In the financial transmission right application, an investigation is made of how generators' ownership of financial transmission rights may influence the effects of the transmission lines on competition. In the second application, the ramp rate constraints of generators are explicitly modeled using a dynamic game framework, and the equilibrium is characterized as the Markov perfect equilibrium. Finally, the strategic behavior of market participants in electricity capacity markets is analyzed and it is shown that the market participants may exaggerate their available capacity in a Nash equilibrium. It is also shown that the more conservative the independent system operator's capacity procurement, the higher the risk of exaggerated capacity offers.

  5. Steady state security assessment in deregulated power systems

    NASA Astrophysics Data System (ADS)

    Manjure, Durgesh Padmakar

    Power system operations are undergoing changes, brought about primarily due to deregulation and subsequent restructuring of the power industry. The primary intention of the introduction of deregulation in power systems was to bring about competition and improved customer focus. The underlying motive was increased economic benefit. Present day power system analysis is much different than what it was earlier, essentially due to the transformation of the power industry from being cost-based to one that is price-based and due to open access of transmission networks to the various market participants. Power is now treated as a commodity and is traded in an open market. The resultant interdependence of the technical criteria and the economic considerations has only accentuated the need for accurate analysis in power systems. The main impetus in security analysis studies is on efficient assessment of the post-contingency status of the system, accuracy being of secondary consideration. In most cases, given the time frame involved, it is not feasible to run a complete AC load flow for determining the post-contingency state of the system. Quite often, it is not warranted as well, as an indication of the state of the system is desired rather than the exact quantification of the various state variables. With the inception of deregulation, transmission networks are subjected to a host of multilateral transactions, which would influence physical system quantities like real power flows, security margins and voltage levels. For efficient asset utilization and maximization of the revenue, more often than not, transmission networks are operated under stressed conditions, close to security limits. Therefore, a quantitative assessment of the extent to which each transaction adversely affects the transmission network is required. This needs to be done accurately as the feasibility of the power transactions and subsequent decisions (execution, curtailment, pricing) would depend upon the

  6. Ras-Mediated Deregulation of the Circadian Clock in Cancer

    PubMed Central

    Relógio, Angela; Thomas, Philippe; Medina-Pérez, Paula; Reischl, Silke; Bervoets, Sander; Gloc, Ewa; Riemer, Pamela; Mang-Fatehi, Shila; Maier, Bert; Schäfer, Reinhold; Leser, Ulf; Herzel, Hanspeter; Kramer, Achim; Sers, Christine

    2014-01-01

    Circadian rhythms are essential to the temporal regulation of molecular processes in living systems and as such to life itself. Deregulation of these rhythms leads to failures in biological processes and eventually to the manifestation of pathological phenotypes including cancer. To address the questions as to what are the elicitors of a disrupted clock in cancer, we applied a systems biology approach to correlate experimental, bioinformatics and modelling data from several cell line models for colorectal and skin cancer. We found strong and weak circadian oscillators within the same type of cancer and identified a set of genes, which allows the discrimination between the two oscillator-types. Among those genes are IFNGR2, PITX2, RFWD2, PPARγ, LOXL2, Rab6 and SPARC, all involved in cancer-related pathways. Using a bioinformatics approach, we extended the core-clock network and present its interconnection to the discriminative set of genes. Interestingly, such gene signatures link the clock to oncogenic pathways like the RAS/MAPK pathway. To investigate the potential impact of the RAS/MAPK pathway - a major driver of colorectal carcinogenesis - on the circadian clock, we used a computational model which predicted that perturbation of BMAL1-mediated transcription can generate the circadian phenotypes similar to those observed in metastatic cell lines. Using an inducible RAS expression system, we show that overexpression of RAS disrupts the circadian clock and leads to an increase of the circadian period while RAS inhibition causes a shortening of period length, as predicted by our mathematical simulations. Together, our data demonstrate that perturbations induced by a single oncogene are sufficient to deregulate the mammalian circadian clock. PMID:24875049

  7. Deregulation 1993: Be careful what you wish for, you might get it

    SciTech Connect

    Scotto, D.

    1993-05-01

    This article tries to assess the response at the electric industry to deregulation. The industry most probably will consolidate to reduce operating costs and expand access to other transmission grids. In addition, the cheapest power likely will be [open quotes]dedicated[close quotes] to retail customers (namely, those under a franchise obligation), and [open quotes]residual[close quotes] generating capacity will be placed in the wholesale market. Surplus capacity (the most expensive capacity) could be dedicated to the wholesale sector, allowing market forces to decide the future price of incremental generation. The outcome will be influenced heavily by corporate restructuring initiatives, regulatory willingness or opposition, legal victories by large-scale users, and transmission access policies at the state and federal levels. Changes is definitely underway, but [open quotes]what[close quotes] the industry will look like is unclear. The financial consequences of this change are more easily identified. Evidently, internal pricing pressures and the breakdown of regulatory pricing structures (a trend that has been underway for nearly a decade) have combined to produce a more risky industry. To compensate investors, capital markets could demand increases returns and different corporate structures. Many of the financial benefits currently enjoyed by utilities, such as lower earnings/coverage tests and greater debt leverage than other [open quotes]industrial[close quotes] corporations, may have to change. Stepping out from under the protection of the regulatory umbrella will carry certain costs.

  8. 76 FR 6759 - Monsanto Company and KWS SAAT AG; Decision With Respect to the Petition for Partial Deregulation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-08

    ... Petition for Partial Deregulation of Genetically Engineered Roundup Ready Sugar Beets AGENCY: Animal and... decision to ``partially deregulate'' Roundup Ready sugar beets developed by the Monsanto Company (Monsanto... root crop production activities when conducted under certain mandatory conditions. APHIS has...

  9. [Hypothalamic inflammation and energy balance deregulations: focus on chemokines.

    PubMed

    Le Thuc, Ophélia; Rovère, Carole

    2016-01-01

    The hypothalamus is a key brain region in the regulation of energy balance. It especially controls food intake and both energy storage and expenditure through integration of humoral, neural and nutrient-related signals and cues. Hypothalamic neurons and glial cells act jointly to orchestrate, both spatially and temporally, regulated metabolic functions of the hypothalamus. Thus, the existence of a causal link between hypothalamic inflammation and deregulations of feeding behavior, such as involuntary weight-loss or obesity, has been suggested. Among the inflammatory mediators that could induce deregulations of hypothalamic control of the energy balance, chemokines represent interesting candidates. Indeed, chemokines, primarily known for their chemoattractant role of immune cells to the inflamed site, have also been suggested capable of neuromodulation. Thus, chemokines could disrupt cellular activity together with synthesis and/or secretion of multiple neurotransmitters/mediators that are involved in the maintenance of energy balance. Here, we relate, on one hand, recent results showing the primary role of the central chemokinergic signaling CCL2/CCR2 for metabolic and behavioral adaptation to high-grade inflammation, especially loss of appetite and weight, through its activity on hypothalamic neurons producing the orexigenic peptide Melanin-Concentrating Hormone (MCH) and, on the other hand, results that suggest that chemokines could also deregulate hypothalamic neuropeptidergic circuits to induce an opposite phenotype and eventually participate in the onset/development of obesity. In more details, we will emphasize a study recently showing, in a model of high-grade acute inflammation of LPS injection in mice, that central CCL2/CCR2 signaling is of primary importance for several aspects explaining weight loss associated with inflammation: after LPS injection, animals lose weight, reduce their food intake, increase their fat oxidation (thus energy consumption from

  10. Electricity generation and transmission planning in deregulated power markets

    NASA Astrophysics Data System (ADS)

    He, Yang

    This dissertation addresses the long-term planning of power generation and transmission facilities in a deregulated power market. Three models with increasing complexities are developed, primarily for investment decisions in generation and transmission capacity. The models are presented in a two-stage decision context where generation and transmission capacity expansion decisions are made in the first stage, while power generation and transmission service fees are decided in the second stage. Uncertainties that exist in the second stage affect the capacity expansion decisions in the first stage. The first model assumes that the electric power market is not constrained by transmission capacity limit. The second model, which includes transmission constraints, considers the interactions between generation firms and the transmission network operator. The third model assumes that the generation and transmission sectors make capacity investment decisions separately. These models result in Nash-Cournot equilibrium among the unregulated generation firms, while the regulated transmission network operator supports the competition among generation firms. Several issues in the deregulated electric power market can be studied with these models such as market powers of generation firms and transmission network operator, uncertainties of the future market, and interactions between the generation and transmission sectors. Results deduced from the developed models include (a) regulated transmission network operator will not reserve transmission capacity to gain extra profits; instead, it will make capacity expansion decisions to support the competition in the generation sector; (b) generation firms will provide more power supplies when there is more demand; (c) in the presence of future uncertainties, the generation firms will add more generation capacity if the demand in the future power market is expected to be higher; and (d) the transmission capacity invested by the

  11. [Deregulation and equity: the Obras Sociales reconversion process in Argentina].

    PubMed

    Findling, Liliana; Arrunada, María; Klimovsky, Ezequiel

    2002-01-01

    The health care services managed by trade unions and known as "Obras Sociales" form the groundwork for Argentina's Social Security and Health system. However, far from taking an equitable approach, these institutions highlight the country's prevailing income disparities, which in turn lead to major differences in access to care. The main focus of this study was the reformulation of social security health policies within the framework of deregulation from 1998 to 2000, analyzing the effects on availability of health care services from an equity perspective. The methodology used two related analytical levels: (1) a macro level viewing the process from the various players' strategies and (2) a micro level featuring the changes within a well-known trade union social security organization during its reconversion process, emphasizing its institutional scope and the opinions of its membership. The results thus pointed to the slow implementation of reforms initiated by the public sector, hindered by constant negotiations among the main corporate actors seeking to serve their particular interests, along with increased inequity and fragmentation due to the limited opening of free choice by members.

  12. Deregulation of dicer and mir-155 expression in liposarcoma

    PubMed Central

    Vincenzi, Bruno; Iuliani, Michele; Zoccoli, Alice; Pantano, Francesco; Fioramonti, Marco; De Lisi, Delia; Frezza, Anna Maria; Rabitti, Carla; Perrone, Giuseppe; Muda, Andrea Onetti; Russo, Antonio; Giordano, Antonio; Santini, Daniele; Dei Tos, Angelo Paolo; Tonini, Giuseppe

    2015-01-01

    Liposarcoma (LPS) is the most common soft tissue sarcoma. It has been demonstrated that mir-155 was the most overexpressed miRNA in well-differentiated LPS(WDLPS)/dedifferentiated LPS (DDLPS). The aim of this study is to evaluate the involvement of Dicer, Drosha and mir-155 in development of LPS and their possible role in stratification of different histological subtypes. Dicer, Drosha and mir-155 mRNA levels were analyzed in formalin-fixed paraffin-embedded specimens from patients diagnosed with 62 LPS and compared with samples of adipose tissues of healthy donors. The experimental data were obtained using qRT-PCR comparing Dicer, Drosha and mir-155 expression levels in tumor samples versus normal fat. The tumor samples from LPS patients showed a significantly lower Dicer expression versus normal adipose tissue, while Drosha levels did not differ. Concerning mir155 expression levels, our results demonstrated a significant mir-155 up-regulation in all LPS subtypes versus normal adipose tissue except for WDLS. These findings demonstrate for the first time that Dicer is deregulated in LPS and show that mir-155 is differentially expressed in LPS subgroups and it could be a promising tool to improve LPS disease stratification and differential diagnosis. PMID:25888631

  13. Power system market implementation in a deregulated environment

    NASA Astrophysics Data System (ADS)

    Silva, Carlos

    2000-10-01

    The opening of the power system markets (also known as deregulation) gives rise to issues never seen before by this industry. One of the most important is the control of information about the cost of generation. Information that used to be common knowledge is now kept private by the new agents of the system (generator companies, distribution companies, etc.). Data such as the generator cost functions are now known only by the owning companies. The result is a new system consisting of a group of independent firms seeking the maximization of their own profit. There have been many proposals to organize the new market in an economically efficient manner. Nevertheless, the uniqueness of the electric power system has prevented the development of such a market. This thesis evaluates the most common proposals using simulations in an auction setting. In addition a new methodology is proposed based on mechanism design, a common technique in economics, that solves some of the practical problems of power system markets (such as the management of limited transmission capacity). In this methodology, when each company acts in its best interest, the outcome is efficient in spite of the information problem cited above. This new methodology, along with the existing methodologies, are tested using simulation and analyzed to create a clear comparison of benefits and disadvantages.

  14. Hypermutation of DPYD Deregulates Pyrimidine Metabolism and Promotes Malignant Progression

    PubMed Central

    Edwards, Lauren; Gupta, Rohit; Filipp, Fabian V.

    2016-01-01

    New strategies are needed to diagnose and target human melanoma. To this end, genomic analyses was performed to assess somatic mutations and gene expression signatures using a large cohort of human skin cutaneous melanoma (SKCM) patients from The Cancer Genome Atlas (TCGA) project to identify critical differences between primary and metastatic tumors. Interestingly, pyrimidine metabolism is one of the major pathways to be significantly enriched and deregulated at the transcriptional level in melanoma progression. In addition, dihydropyrimidine dehydrogenase (DPYD) and other important pyrimidine-related genes: DPYS, AK9, CAD, CANT1, ENTPD1, NME6, NT5C1A, POLE, POLQ, POLR3B, PRIM2, REV3L, and UPP2 are significantly enriched in somatic mutations relative to the background mutation rate. Structural analysis of the DPYD protein dimer reveals a potential hotspot of recurring somatic mutations in the ligand binding sites as well as the interfaces of protein domains that mediated electron transfer. Somatic mutations of DPYD are associated with upregulation of pyrimidine degradation, nucleotide synthesis, and nucleic acid processing while salvage and nucleotide conversion is downregulated in TCGA SKCM. PMID:26609109

  15. Deregulation of lipid metabolism pathway genes in nasopharyngeal carcinoma cells

    PubMed Central

    DAKER, MAELINDA; BHUVANENDRAN, SAATHEEYAVAANE; AHMAD, MUNIRAH; TAKADA, KENZO; KHOO, ALAN SOO-BENG

    2012-01-01

    Nasopharyngeal carcinoma (NPC) is a unique tumour of epithelial origin with a distinct geographical distribution, closely associated with the Epstein-Barr virus (EBV). EBV-encoded RNAs (EBERs) are small non-polyadenylated RNAs that are abundantly expressed in latent EBV-infected NPC cells. To study the role of EBERs in NPC, we established stable expression of EBERs in HK1, an EBV-negative NPC cell line. Cells expressing EBERs consistently exhibited an increased growth rate. However, EBERs did not confer resistance towards cisplatin-induced apoptosis or promote migration or invasion ability in the cells tested. Using microarray gene expression profiling, we identified potential candidate genes that were deregulated in NPC cells expressing EBERs. Gene Ontology analysis of the data set revealed that EBERs upregulate the cellular lipid metabolic process. Upregulation of low-density lipoprotein receptor (LDLR) and fatty acid synthase (FASN) was observed in EBER-expressing cells. NPC cells exhibited LDL-dependent cell proliferation. In addition, a polyphenolic flavonoid compound, quercetin, known to inhibit FASN, was found to inhibit proliferation of NPC cells. PMID:23292678

  16. Issues in the deregulation of the electric industry

    NASA Astrophysics Data System (ADS)

    Tyler, Cleve Brent

    The electric industry is undergoing a major restructuring which allows competition in the generation portion of the industry. This dissertation explores several pricing issues relevant to this restructuring. First, an extensive overview examines the industry's history, discusses major regulation theories, and relays the major issues of deregulation. Second, a literature review recounts major works in the economics literature on price discrimination, pricing efficiency, and cost estimation. Then, customer specific generation, transmission, distribution, and general and administration costs are estimated for each company. The customer classes are residential, general service, large general service, and large industrial, representing a finer division of customer classes than found in previous studies. Average prices are compiled and marginal prices are determined from a set of utility schedules. Average and marginal price/cost ratios are computed for each customer class. These ratios show that larger use customers face relative price discrimination but operate under more efficient price structures than small use consumers. Finally, issues in peak load pricing are discussed using a model which predicts inefficient capital choice by regulated utilities. Efficiency losses are estimated to be $620 million dollars a year from the lack of peak load prices under regulation. This result is based on the time-of-use pricing predictions from the Department of Energy.

  17. Effects of the Deregulation on the Concentration of the Brazilian Air Transportation Industry

    NASA Technical Reports Server (NTRS)

    Guterres, Marcelo Xavier; Muller, Carlos

    2003-01-01

    This paper addresses the effects of the deregulation of the Brazilian air transportation industry in terms of the concentration of the market. We will show some metrics that are commonly used to study the concentration of the industry. This paper uses the Herfindhal- Hirschman Index. This index tends to zero in the competitive scenario, with a large number of small firms, and to one in case of a monopolistic scenario. The paper analyses the dynamics of the concentration of the Brazilian domestic air transportation market, in order to evaluate the effects of deregulation. We conclude that the Brazilian market presents oligopoly characteristics and aspects in its current structure that maintain the market concentrated in spite of the Deregulation measures adopted by the aeronautical authority. Keywords: Herfindhal-Hirschman Index, concentration, Deregulation

  18. Fuel, environmental, and transmission pricing considerations in a deregulated environment

    NASA Astrophysics Data System (ADS)

    Obessis, Emmanouil Vlassios

    The 1992 National Energy Policy Act drastically changed the traditional structure of the vertically integrated utility. To facilitate increased competition in the power utility sector, all markets related to power generation have been opened to free competition and trading. To survive in the new competitive environment, power producers need to reduce costs and increase efficiency. Fuel marketing strategies are thus, getting more aggressive and fuel markets are becoming more competitive, offering more options regarding fuel supplies and contracts. At the same time, the 1990 Clean Air Act Amendments are taking effect. Although tightening the emission standards, this legislation offers utilities a wider flexibility in choosing compliance strategies. It also set maximum annual allowable levels replacing the traditional uniform maximum emission rates. The bill also introduced the concept of marketable emission allowances and provided for the establishment of nationwide markets where allowances may be traded, sold, or purchased. Several fuel- and emission-constrained algorithms have been historically presented, but those two classes of constraints, in general, were handled independently. The multiobjective optimization model developed in this research work, concurrently satisfies sets of detailed fuel and emission limits, modeling in a more accurate way the fuel supply and environmental limitations and their complexities in the new deregulated operational environment. Development of the implementation software is an integral part of this research project. This software may be useful for both daily scheduling activities and short-term operational planning. A Lagrangian multipliers-based variant is used to solve the problem. Single line searches are used to update the multipliers, thus offering attractive execution times. This work also investigates the applicability of cooperative games to the problem of transmission cost allocation. Interest in game theory as a powerful

  19. EGFR gene deregulation mechanisms in lung adenocarcinoma: A molecular review.

    PubMed

    Tsiambas, Evangelos; Lefas, Alicia Y; Georgiannos, Stavros N; Ragos, Vasileios; Fotiades, Panagiotis P; Grapsa, Dimitra; Stamatelopoulos, Athanasios; Kavantzas, Nikolaos; Patsouris, Efstratios; Syrigos, Konstantinos

    2016-08-01

    For the last two decades, evolution in molecular biology has expanded our knowledge in decoding a broad spectrum of genomic imbalances that progressively lead normal cells to a neoplastic state and finally to complete malignant transformation. Concerning oncogenes and signaling transduction pathways mediated by them, identification of specific gene alterations remains a critical process for handling patients by applying targeted therapeutic regimens. The epidermal growth factor receptor (EGFR) signaling pathway plays a crucial role in regulating cell proliferation, differentiation and apoptosis in normal cells. EGFR mutations and amplification represent the gene's main deregulation mechanisms in cancers of different histo-genetic origin. Furthermore, intra-cancer molecular heterogeneity due to clonal rise and expansion mainly explains the variable resistance to novel anti-EGFR monoclonal antibody (mAb), and also tyrosine kinase inhibitors (TKIs). According to recently published 2015 WHO new classification, lung cancer is the leading cause of death related to cancer and its incidence is still on the increase worldwide. The majority of patients suffering from lung cancer are diagnosed with epithelial tumors (adenocarcinoma predominantly and squamous cell carcinoma represent ∼85% of all pathologically defined lung cancer cases). In those patients, EGFR-activating somatic mutations in exons 18/19/20/21 modify patients' sensitivity (i.e. exon 21 L858R, exon 19 LREA deletion) or resistance (ie exon 20 T790M and/or insertion) to TKI mediated targeted therapeutic strategies. Additionally, the role of specific micro-RNAs that affect EGFR regulation is under investigation. In the current review, we focused on EGFR gene/protein structural and functional aspects and the corresponding alterations that occur mainly in lung adenocarcinoma to critically modify its molecular landscape.

  20. Analysis of Polymorphisms in Genes (AGT, MTHFR, GPIIIa, and GSTP1) Associated with Hypertension, Thrombophilia and Oxidative Stress in Mestizo and Amerindian Populations of México

    PubMed Central

    Juárez-Velázquez, Rocio; Canto, Patricia; Canto-Cetina, Thelma; Rangel-Villalobos, Hector; Rosas-Vargas, Haydee; Rodríguez, Maricela; Canizales-Quinteros, Samuel; Velázquez Wong, Ana Claudia; Ordoñez-Razo, Rosa María; Vilchis-Dorantes, Guadalupe; Coral-Vázquez, Ramón Mauricio

    2010-01-01

    Several polymorphisms related to hypertension, thrombophilia, and oxidative stress has been associated with the development of cardiovascular disease. We analyzed the frequency of M235T angiotensinogen (AGT), A222V 5,10 methylenete-trahydrofolate reductase (MTHFR), L33P glycoprotein IIIa (GPIIIa), and I105V glutathione S-transferase P1 (GSTP1) polymorphisms in 285 individuals belonging to Mexican-Mestizo and five Amerindian population from México, by real time PCR allelic discrimination. Allele and genotype frequencies were compared using χ2 tests. All populations followed the Hardy Weinberg equilibrium for assay markers with the exception of the Triki, whose were in Hardy Weinberg dysequilibrium for the glutathione S-transferase P1 polymorphism. Interestingly, according to all the analyzed single nucleotide polymorphisms (SNPs), the Triki population was the most differentiated and homogeneous group of the six populations analyzed. A comparison of our data with those previously published for some Caucasian, Asian and Black populations showed quite significant differences. These differences were remarkable with all the Mexican populations having a lower frequency of the 105V allele of the glutathione S-transferase P1 and reduced occurrence of the 222A allele of the 5,10 methylenetetrahydrofolate reductase. Our results show the genetic diversity among different Mexican populations and with other racial groups. PMID:20592457

  1. FAA (Federal Aviation Administration) Aviation Forecasts - Fiscal Years 1984-1995,

    DTIC Science & Technology

    1984-02-01

    available to the public Taxi, Aviation Activity Forecasts, through the National Technical Comuters, Federal Aviation Administra- Information Service , tion...statutory mission, that being " service to the Nation by providing a safe and efficient aviation system which contributes to national security and the...proved insufficient to justify regularly scheduled service . Airline deregulation has accelerated this process with the Majors and Nationals concentrating

  2. The Federal Communications Commission and the Fairness Doctrine: Public Interest Failure?

    ERIC Educational Resources Information Center

    Jung, Donald J.

    Arguing that the Federal Communications Commission's (FCC) decision abolishing the Fairness Doctrine rested on unquestionable and untestable ideological assumptions, this paper asserts that the FCC has pursued broadcast deregulation with inadequate consideration of either social scientists' knowledge about the news media and their audiences, and…

  3. Posttranscriptional deregulation of signaling pathways in meningioma subtypes by differential expression of miRNAs

    PubMed Central

    Ludwig, Nicole; Kim, Yoo-Jin; Mueller, Sabine C.; Backes, Christina; Werner, Tamara V.; Galata, Valentina; Sartorius, Elke; Bohle, Rainer M.; Keller, Andreas; Meese, Eckart

    2015-01-01

    Background Micro (mi)RNAs are key regulators of gene expression and offer themselves as biomarkers for cancer development and progression. Meningioma is one of the most frequent primary intracranial tumors. As of yet, there are limited data on the role of miRNAs in meningioma of different histological subtypes and the affected signaling pathways. Methods In this study, we compared expression of 1205 miRNAs in different meningioma grades and histological subtypes using microarrays and independently validated deregulation of selected miRNAs with quantitative real-time PCR. Clinical utility of a subset of miRNAs as biomarkers for World Health Organization (WHO) grade II meningioma based on quantitative real-time data was tested. Potential targets of deregulated miRNAs were discovered with an in silico analysis. Results We identified 13 miRNAs deregulated between different subtypes of benign meningiomas, and 52 miRNAs deregulated in anaplastic meningioma compared with benign meningiomas. Known and putative target genes of deregulated miRNAs include genes involved in epithelial-to-mesenchymal transition for benign meningiomas, and Wnt, transforming growth factor–β, and vascular endothelial growth factor signaling for higher-grade meningiomas. Furthermore, a 4-miRNA signature (miR-222, -34a*, -136, and -497) shows promise as a biomarker differentiating WHO grade II from grade I meningiomas with an area under the curve of 0.75. Conclusions Our data provide novel insights into the contribution of miRNAs to the phenotypic spectrum in benign meningiomas. By deregulating translation of genes belonging to signaling pathways known to be important for meningioma genesis and progression, miRNAs provide a second in line amplification of growth promoting cellular signals. MiRNAs as biomarkers for diagnosis of aggressive meningiomas might prove useful and should be explored further in a prospective manner. PMID:25681310

  4. Escape from Cbl-mediated downregulation: a recurrent theme for oncogenic deregulation of receptor tyrosine kinases.

    PubMed

    Peschard, Pascal; Park, Morag

    2003-06-01

    Deregulation of growth factor receptor tyrosine kinases (RTKs) is linked to a large number of malignancies. This occurs through a variety of mechanisms that result in enhanced activity of the receptor. Considerable evidence now supports the idea that loss of negative regulation plays an important role in receptor deregulation. RTKs are removed from the cell surface via endocytosis and many are subsequently degraded in the lysosome. Lysosomal targeting has recently been linked with receptor ubiquitination. We review here molecular alterations that uncouple RTKs from ubiquitination and implicate loss of ubiquitination as a process that plays a significant role in the pathogenesis of cancer.

  5. An integer linear programming approach for finding deregulated subgraphs in regulatory networks.

    PubMed

    Backes, Christina; Rurainski, Alexander; Klau, Gunnar W; Müller, Oliver; Stöckel, Daniel; Gerasch, Andreas; Küntzer, Jan; Maisel, Daniela; Ludwig, Nicole; Hein, Matthias; Keller, Andreas; Burtscher, Helmut; Kaufmann, Michael; Meese, Eckart; Lenhof, Hans-Peter

    2012-03-01

    Deregulation of cell signaling pathways plays a crucial role in the development of tumors. The identification of such pathways requires effective analysis tools that facilitate the interpretation of expression differences. Here, we present a novel and highly efficient method for identifying deregulated subnetworks in a regulatory network. Given a score for each node that measures the degree of deregulation of the corresponding gene or protein, the algorithm computes the heaviest connected subnetwork of a specified size reachable from a designated root node. This root node can be interpreted as a molecular key player responsible for the observed deregulation. To demonstrate the potential of our approach, we analyzed three gene expression data sets. In one scenario, we compared expression profiles of non-malignant primary mammary epithelial cells derived from BRCA1 mutation carriers and of epithelial cells without BRCA1 mutation. Our results suggest that oxidative stress plays an important role in epithelial cells of BRCA1 mutation carriers and that the activation of stress proteins may result in avoidance of apoptosis leading to an increased overall survival of cells with genetic alterations. In summary, our approach opens new avenues for the elucidation of pathogenic mechanisms and for the detection of molecular key players.

  6. Internationalization, Deregulation and the Extension of Higher Education in Korea: A Further Note

    ERIC Educational Resources Information Center

    Jin, Jang C.

    2015-01-01

    The Korean government implemented several educational policies to enhance internationalization of higher education such as deregulation of higher education, classroom instructions in English, and faculty publications in international refereed journals. However, the speed of globalization has been lagging behind (Green, 2015). Alternatively, this…

  7. Electric Deregulation: Don't Get the Cart before the Horse.

    ERIC Educational Resources Information Center

    Schaeffer, Statton C.

    1999-01-01

    Examines the development of a campus energy-monitoring system and three energy strategies to help control energy costs in a deregulated environment. Strategies discussed involve purchasing off-campus electric energy, modifying power-plant technology, and considering third-party ownership of the power plant. (GR)

  8. Deregulating the electric utility industry: financial dislocations and implicit regulatory rents

    SciTech Connect

    Golub, B.W.

    1982-01-01

    A framework was developed that lends itself to both order-of-magnitude estimates of the aggregate impact of deregulation and an approach to structuring the debate about the equity of the financial dislocations that deregulation will create. This approach involves calculating what one can term implicit regulatory rents. Implicit regulatory rents are the present value of regulatory policies that cause derivations from outcomes consistent with long-run competitive equilibrium. Using this approach, it was found that up to $196 billion dollars in present value might be transferred from customers to existing utilities through the loss of implicit regulatory rents. This figure is not, however, appropriate for use as a substitute for the financial dislocations referred to above. It permits two important observations: (1) deregulation of the electric utility industry does have the potential to create huge financial gains and losses; and (2) any deregulation proposal must be concerned with the details of the prior regulatory regime since some very large sums of money, such as deferred taxes and outstanding long-term bonds, may mean very different things depending upon how the regulatory process defined them. A financial simulation model is used to illustrate how implicit regulatory rents can be calculated at the level of an individual firm. 51 references.

  9. The Italian Middle School in a Deregulation Era: Modernity through Path-Dependency and Global Models

    ERIC Educational Resources Information Center

    Mincu, Monica E.

    2015-01-01

    In the current context of intensified moves towards educational deregulation, the configuration of the Italian middle school and its relationship to education governance is an interesting case. Historically, it represents a unique example of the successful "decision-making" model of the welfarist era. Despite some internal constraints,…

  10. Short-Term Effects of State Deregulation on the Adequacy and Equity of School Facility Projects.

    ERIC Educational Resources Information Center

    Kowalski, Theodore J.; Decman, John C.

    2002-01-01

    In 1995, the Indiana Legislature deregulated state controls over public-school construction projects by reducing the status of required specifications to guidelines. Also, local taxpayers were given greater authority to prevent proposed projects. This study examines the short-term effects of this policy shift. (Contains 5 tables and 16…

  11. Internationalization, Deregulation and the Expansion of Higher Education in Korea: An Historical Overview

    ERIC Educational Resources Information Center

    Green, Christopher

    2015-01-01

    The purpose of this article is to provide an overview of internationalization policies in Korean higher education since 1993. Deregulation was a key strategy of Korean governments, but this strategy has led to an increasing oversupply of enrolment capacity. In response, the current government is implementing a system of reregulation to reduce the…

  12. Job Placement in Germany: Developments before and after Deregulation. IAB Labour Market Research Topics No. 31.

    ERIC Educational Resources Information Center

    Walwei, Ulrich

    Since 1994, the German public employment service has not had a monopoly on placement. A new law permits private job placement as an independent activity, but only with a license from the public employment service. Since deregulation, the number of job placement licenses has increased continuously, but the number of placements made by private…

  13. Federated Giovanni

    NASA Technical Reports Server (NTRS)

    Lynnes, C.

    2014-01-01

    Federated Giovanni is a NASA-funded ACCESS project to extend the scope of the GES DISC Giovanni online analysis tool to 4 other Distributed Active Archive Centers within EOSDIS: OBPG, LP-DAAC, MODAPS and PO.DAAC. As such, it represents a significant instance of sharing technology across the DAACs. We also touch on several sub-areas that are also sharable, such as Giovanni URLs, workflows and OGC-accessible services.

  14. Analysis of Deregulated microRNAs and Their Target Genes in Gastric Cancer

    PubMed Central

    Kupcinskas, Juozas; Link, Alexander; Kiudelis, Gediminas; Jonaitis, Laimas; Jarmalaite, Sonata; Kupcinskas, Limas; Malfertheiner, Peter; Skieceviciene, Jurgita

    2015-01-01

    Background MicroRNAs (miRNAs) are widely studied non-coding RNAs that modulate gene expression. MiRNAs are deregulated in different tumors including gastric cancer (GC) and have potential diagnostic and prognostic implications. The aim of our study was to determine miRNA profile in GC tissues, followed by evaluation of deregulated miRNAs in plasma of GC patients. Using available databases and bioinformatics methods we also aimed to evaluate potential target genes of confirmed differentially expressed miRNA and validate these findings in GC tissues. Methods The study included 51 GC patients and 51 controls. Initially, we screened miRNA expression profile in 13 tissue samples of GC and 12 normal gastric tissues with TaqMan low density array (TLDA). In the second stage, differentially expressed miRNAs were validated in a replication cohort using qRT-PCR in tissue and plasma samples. Subsequently, we analyzed potential target genes of deregulated miRNAs using bioinformatics approach, determined their expression in GC tissues and performed correlation analysis with targeting miRNAs. Results Profiling with TLDA revealed 15 deregulated miRNAs in GC tissues compared to normal gastric mucosa. Replication analysis confirmed that miR-148a-3p, miR-204-5p, miR-223-3p and miR-375 were consistently deregulated in GC tissues. Analysis of GC patients’ plasma samples showed significant down-regulation of miR-148a-3p, miR-375 and up-regulation of miR-223-3p compared to healthy subjects. Further, using bioinformatic tools we identified targets of replicated miRNAs and performed disease-associated gene enrichment analysis. Ultimately, we evaluated potential target gene BCL2 and DNMT3B expression by qRT-PCR in GC tissue, which correlated with targeting miRNA expression. Conclusions Our study revealed miRNA profile in GC tissues and showed that miR-148a-3p, miR-223-3p and miR-375 are deregulated in GC plasma samples, but these circulating miRNAs showed relatively weak diagnostic

  15. Molecular Mechanisms of p53 Deregulation in Cancer: An Overview in Multiple Myeloma

    PubMed Central

    Herrero, Ana B.; Rojas, Elizabeta A.; Misiewicz-Krzeminska, Irena; Krzeminski, Patryk; Gutiérrez, Norma C.

    2016-01-01

    The p53 pathway is inactivated in the majority of human cancers. Although this perturbation frequently occurs through the mutation or deletion of p53 itself, there are other mechanisms that can attenuate the pathway and contribute to tumorigenesis. For example, overexpression of important p53 negative regulators, such as murine double minute 2 (MDM2) or murine double minute 4 (MDM4), epigenetic deregulation, or even alterations in TP53 mRNA splicing. In this work, we will review the different mechanisms of p53 pathway inhibition in cancer with special focus on multiple myeloma (MM), the second most common hematological malignancy, with low incidence of p53 mutations/deletions but growing evidence of indirect p53 pathway deregulation. Translational implications for MM and cancer prognosis and treatment are also reviewed. PMID:27916892

  16. Molecular Mechanisms of p53 Deregulation in Cancer: An Overview in Multiple Myeloma.

    PubMed

    Herrero, Ana B; Rojas, Elizabeta A; Misiewicz-Krzeminska, Irena; Krzeminski, Patryk; Gutiérrez, Norma C

    2016-11-30

    The p53 pathway is inactivated in the majority of human cancers. Although this perturbation frequently occurs through the mutation or deletion of p53 itself, there are other mechanisms that can attenuate the pathway and contribute to tumorigenesis. For example, overexpression of important p53 negative regulators, such as murine double minute 2 (MDM2) or murine double minute 4 (MDM4), epigenetic deregulation, or even alterations in TP53 mRNA splicing. In this work, we will review the different mechanisms of p53 pathway inhibition in cancer with special focus on multiple myeloma (MM), the second most common hematological malignancy, with low incidence of p53 mutations/deletions but growing evidence of indirect p53 pathway deregulation. Translational implications for MM and cancer prognosis and treatment are also reviewed.

  17. Application of games with incomplete information for pricing electricity in deregulated power pools

    SciTech Connect

    Ferrero, R.W.; Rivera, J.F.; Shahidehpour, S.M.

    1998-02-01

    The authors present a game theoretical approach to the problem of pricing electricity in deregulated energy marketplaces. They assume that an Independent System Operator receives bids by Pool participants and defines transactions among participants by looking for the minimum price that satisfies the demand in the Pool. The competition among Pool participants is modeled as a non-cooperative game with incomplete information. They assume that each Pool participant knows its own operation costs but does not know his opponents` operation costs. The game with incomplete information is transformed into a game with complete, but imperfect, information and solved using the Nash equilibrium idea. The approach presented in this paper is geared towards providing support for pricing electricity in deregulated Pools.

  18. Deregulated lncRNAs in B Cells from Patients with Active Tuberculosis

    PubMed Central

    Fu, Yurong; Xu, Xianqin; Xue, Junfang; Duan, Wenping; Yi, Zhengjun

    2017-01-01

    Role of lncRNAs in human adaptive immune response to TB infection is largely unexplored. To address this issue, here we characterized lncRNA expression profile in primary human B cell response to TB infection using microarray assay. Several lncRNAs and mRNAs were chosen for RT-qPCR validation. Bioinformatics prediction was applied to delineate function of the deregulated mRNAs. We found that 844 lncRNAs and 597 mRNAs were differentially expressed between B cell samples from individuals with or without TB. KEGG pathway analysis for the deregulated mRNAs indicated a number of pathways, such as TB, TLR signaling pathway and antigen processing and presentation. Moreover, corresponding to the dysregulation of many lncRNAs, we also found that their adjacent protein-coding genes were also deregulated. Functional annotation for the corresponding mRNAs showed that these lncRNAs were mainly associated with TLR signaling, TGF-β signaling. Interestingly, SOCS3, which is a critical negative regulator of cytokine response to TB infection and its nearby lncRNA XLOC_012582, were highly expressed in active TB B cells. Subsequent RT-qPCR results confirmed the changes. Whether upregulated XLOC_012582 causes SOCS3 overexpression and is eventually involved in the context of exacerbations of active TB represents an interesting issue that deserves to be further explored. Taken together, for the first time, we identified a set of deregulated lncRNAs in active TB B cells and their functions were predicted. Such findings provided novel insight into the pathogenesis of TB and further studies should focus on the function and pathogenic mechanisms of the lncRNAs involved in active TB. PMID:28125665

  19. Identification of Long Non-Coding RNAs Deregulated in Multiple Myeloma Cells Resistant to Proteasome Inhibitors

    PubMed Central

    Malek, Ehsan; Kim, Byung-Gyu; Driscoll, James J.

    2016-01-01

    While the clinical benefit of proteasome inhibitors (PIs) for multiple myeloma (MM) treatment remains unchallenged, dose-limiting toxicities and the inevitable emergence of drug resistance limit their long-term utility. Disease eradication is compromised by drug resistance that is either present de novo or therapy-induced, which accounts for the majority of tumor relapses and MM-related deaths. Non-coding RNAs (ncRNAs) are a broad class of RNA molecules, including long non-coding RNAs (lncRNAs), that do not encode proteins but play a major role in regulating the fundamental cellular processes that control cancer initiation, metastasis, and therapeutic resistance. While lncRNAs have recently attracted significant attention as therapeutic targets to potentially improve cancer treatment, identification of lncRNAs that are deregulated in cells resistant to PIs has not been previously addressed. We have modeled drug resistance by generating three MM cell lines with acquired resistance to either bortezomib, carfilzomib, or ixazomib. Genome-wide profiling identified lncRNAs that were significantly deregulated in all three PI-resistant cell lines relative to the drug-sensitive parental cell line. Strikingly, certain lncRNAs deregulated in the three PI-resistant cell lines were also deregulated in MM plasma cells isolated from newly diagnosed patients compared to healthy plasma cells. Taken together, these preliminary studies strongly suggest that lncRNAs represent potential therapeutic targets to prevent or overcome drug resistance. More investigations are ongoing to expand these initial studies in a greater number of MM patients to better define lncRNAs signatures that contribute to PI resistance in MM. PMID:27782060

  20. Psychology of change: Models and implications for nuclear plants in an era of deregulation

    SciTech Connect

    Gates, W.G.; Stark, J.A.

    1999-09-01

    This presentation explores the psychology of change in the implications that it has for nuclear plants during this era of deregulation. The authors analyze models that work, models that have failed in the past, and specific findings and applications based on 2 yr of research, as well as the results regarding the impact of the psychology of change on the Fort Calhoun nuclear station in Nebraska.

  1. Exts and the AGT Relations

    NASA Astrophysics Data System (ADS)

    Neguţ, Andrei

    2016-09-01

    We prove the connection between the Nekrasov partition function of {N=2} super-symmetric U(2) gauge theory with adjoint matter and conformal blocks for the Virasoro algebra, as predicted by the Alday-Gaiotto-Tachikawa relations. Mathematically, this is achieved by relating the Carlsson-Okounkov Ext vector bundle on the moduli space of rank 2 sheaves with Liouville vertex operators. Our approach is geometric in nature, and uses a new method for intersection-theoretic computations of the Ext operator.

  2. AGT-102 automotive gas turbine

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Development of a gas turbine powertrain with a 30% fuel economy improvement over a comparable S1 reciprocating engine, operation within 0.41 HC, 3.4 CO, and 0.40 NOx grams per mile emissions levels, and ability to use a variety of alternate fuels is summarized. The powertrain concept consists of a single-shaft engine with a ceramic inner shell for containment of hot gasses and support of twin regenerators. It uses a fixed-geometry, lean, premixed, prevaporized combustor, and a ceramic radial turbine rotor supported by an air-lubricated journal bearing. The engine is coupled to the vehicle through a widerange continuously variable transmission, which utilizes gearing and a variable-ratio metal compression belt. A response assist flywheel is used to achieve acceptable levels of engine response. The package offers a 100 lb weight advantage in a Chrysler K Car front-wheel-drive installation. Initial layout studies, preliminary transient thermal analysis, ceramic inner housing structural analysis, and detailed performance analysis were carried out for the basic engine.

  3. The impact of a deregulated European electricity market on Volvo in Sweden

    SciTech Connect

    Dag, S.

    1998-07-01

    The member countries within the European Union (EU) have agreed to open all national electricity markets for competition, starting January 1, 1999. The electricity market in Sweden is deregulated since January 1, 1996. The deregulation of the electricity markets will gradually shift the electricity price levels in different countries towards an equal price level, which will most likely be close to the levels on the Continental Europe. A deregulated European electricity market may change the competition situation for Swedish industries dramatically. The capacity in electric generation with low operating costs in Sweden has led to very low electricity prices and high usage level compared to other EU countries. The consumption level of electric energy per capita is nearly three times higher in Sweden than the average per capita EU usage. The high level of electricity consumption is typical also of industrial customers in Sweden. Studies of Volvo Car Corporation have shown that the Volvo car plant in Torslanda, Sweden utilizes substantially more electric energy per manufactured car than the Volvo car plant in Gent, Belgium. A method is developed to transform the Torslanda plant from a low energy efficiency state to a higher energy efficiency state by modeling. The method is based on the Life Cycle Cost (LCC) concept and includes optimization models of the two plants with mixed integer linear programming (MILP).

  4. The Role of Virus Infection in Deregulating the Cytokine Response to Secondary Bacterial Infection.

    PubMed

    Mehta, Divya; Petes, Carlene; Gee, Katrina; Basta, Sameh

    2015-12-01

    Proinflammatory cytokines are produced by macrophages and dendritic cells (DCs) after infection to stimulate T helper (Th) cells, linking innate and adaptive immunity. Virus infections can deregulate the proinflammatory cytokine response like tumor necrosis factor-α and interleukin (IL)-2, making the host more susceptible to secondary bacterial infections. Studies using various viruses such as lymphocytic choriomeningitis virus, influenza A virus, and human immunodeficiency virus have revealed several intriguing mechanisms that account for the increased susceptibility to several prevalent bacterial infections. In particular, type I interferons induced during a virus infection have been observed to play a role in suppressing the production of some key antibacterial proinflammatory cytokines such as IL-23 and IL-17. Other suppressive mechanisms as a result of cytokine deregulation by viral infections include reduced function of immune cells such as DC, macrophage, natural killer, CD4(+), and CD8(+) T cells leading to impaired clearance of secondary bacterial infections. In this study, we highlight some of the immune mechanisms that become deregulated by viral infections, and can thus become defective during secondary bacterial infections.

  5. Multi-objective Decision Based Available Transfer Capability in Deregulated Power System Using Heuristic Approaches

    NASA Astrophysics Data System (ADS)

    Pasam, Gopi Krishna; Manohar, T. Gowri

    2016-09-01

    Determination of available transfer capability (ATC) requires the use of experience, intuition and exact judgment in order to meet several significant aspects in the deregulated environment. Based on these points, this paper proposes two heuristic approaches to compute ATC. The first proposed heuristic algorithm integrates the five methods known as continuation repeated power flow, repeated optimal power flow, radial basis function neural network, back propagation neural network and adaptive neuro fuzzy inference system to obtain ATC. The second proposed heuristic model is used to obtain multiple ATC values. Out of these, a specific ATC value will be selected based on a number of social, economic, deregulated environmental constraints and related to specific applications like optimization, on-line monitoring, and ATC forecasting known as multi-objective decision based optimal ATC. The validity of results obtained through these proposed methods are scrupulously verified on various buses of the IEEE 24-bus reliable test system. The results presented and derived conclusions in this paper are very useful for planning, operation, maintaining of reliable power in any power system and its monitoring in an on-line environment of deregulated power system. In this way, the proposed heuristic methods would contribute the best possible approach to assess multiple objective ATC using integrated methods.

  6. Epigenetic and genetic deregulation in cancer target distinct signaling pathway domains

    PubMed Central

    Gao, Yang; Teschendorff, Andrew E.

    2017-01-01

    Cancer is characterized by both genetic and epigenetic alterations. While cancer driver mutations and copy-number alterations have been studied at a systems-level, relatively little is known about the systems-level patterns exhibited by their epigenetic counterparts. Here we perform a pan-cancer wide systems-level analysis, mapping candidate cancer-driver DNA methylation (DNAm) alterations onto a human interactome. We demonstrate that functional DNAm alterations in cancer tend to map to nodes of lower connectivity and inter-connectivity, compared to the corresponding alterations at the genomic level. We find that epigenetic alterations are relatively over-represented in extracellular and transmembrane signaling domains, whereas cancer genes undergoing amplification or deletion tend to be enriched within the intracellular domain. A pan-cancer wide meta-analysis identifies WNT and chemokine signaling, as two key pathways where epigenetic deregulation preferentially targets extracellular components. We further pinpoint specific chemokine ligands/receptors whose epigenetic deregulation associates with key epigenetic enzymes, representing potential targets for epigenetic therapy. Our results suggest that epigenetic deregulation in cancer not only targets tissue-specific transcription factors, but also modulates signaling within the extra-cellular domain, providing novel system-level insight into the potential distinctive role of genetic and epigenetic alterations in cancer. PMID:27899617

  7. Deregulation of purine pathway in Bacillus subtilis and its use in riboflavin biosynthesis

    PubMed Central

    2014-01-01

    Background Purine nucleotides are essential metabolites for living organisms because they are involved in many important processes, such as nucleic acid synthesis, energy supply, and biosynthesis of several amino acids and riboflavin. Owing to the pivotal roles of purines in cell physiology, the pool of intracellular purine nucleotides must be maintained under strict control, and hence the de novo purine biosynthetic pathway is tightly regulated by transcription repression and inhibition mechanism. Deregulation of purine pathway is essential for this pathway engineering in Bacillus subtilis. Results Deregulation of purine pathway was attempted to improve purine nucleotides supply, based on a riboflavin producer B. subtilis strain with modification of its rib operon. To eliminate transcription repression, the pur operon repressor PurR and the 5’-UTR of pur operon containing a guanine-sensing riboswitch were disrupted. Quantitative RT-PCR analysis revealed that the relative transcription levels of purine genes were up-regulated about 380 times. Furthermore, site-directed mutagenesis was successfully introduced into PRPP amidotransferase (encoded by purF) to remove feedback inhibition by homologous alignment and analysis. Overexpression of the novel mutant PurF (D293V, K316Q and S400W) significantly increased PRPP amidotransferase activity and triggered a strong refractory effect on purine nucleotides mediated inhibition. Intracellular metabolite target analysis indicated that the purine nucleotides supply in engineered strains was facilitated by a stepwise gene-targeted deregulation. With these genetic manipulations, we managed to enhance the metabolic flow through purine pathway and consequently increased riboflavin production 3-fold (826.52 mg/L) in the purF-VQW mutant strain. Conclusions A sequential optimization strategy was applied to deregulate the rib operon and purine pathway of B. subtilis to create genetic diversities and to improve riboflavin production

  8. Multi-Objective Differential Evolution for Voltage Security Constrained Optimal Power Flow in Deregulated Power Systems

    NASA Astrophysics Data System (ADS)

    Roselyn, J. Preetha; Devaraj, D.; Dash, Subhransu Sekhar

    2013-11-01

    Voltage stability is an important issue in the planning and operation of deregulated power systems. The voltage stability problems is a most challenging one for the system operators in deregulated power systems because of the intense use of transmission line capabilities and poor regulation in market environment. This article addresses the congestion management problem avoiding offline transmission capacity limits related to voltage stability by considering Voltage Security Constrained Optimal Power Flow (VSCOPF) problem in deregulated environment. This article presents the application of Multi Objective Differential Evolution (MODE) algorithm to solve the VSCOPF problem in new competitive power systems. The maximum of L-index of the load buses is taken as the indicator of voltage stability and is incorporated in the Optimal Power Flow (OPF) problem. The proposed method in hybrid power market which also gives solutions to voltage stability problems by considering the generation rescheduling cost and load shedding cost which relieves the congestion problem in deregulated environment. The buses for load shedding are selected based on the minimum eigen value of Jacobian with respect to the load shed. In the proposed approach, real power settings of generators in base case and contingency cases, generator bus voltage magnitudes, real and reactive power demands of selected load buses using sensitivity analysis are taken as the control variables and are represented as the combination of floating point numbers and integers. DE/randSF/1/bin strategy scheme of differential evolution with self-tuned parameter which employs binomial crossover and difference vector based mutation is used for the VSCOPF problem. A fuzzy based mechanism is employed to get the best compromise solution from the pareto front to aid the decision maker. The proposed VSCOPF planning model is implemented on IEEE 30-bus system, IEEE 57 bus practical system and IEEE 118 bus system. The pareto optimal

  9. Deregulation of apoplastic polyamine oxidase affects development and salt response of tobacco plants.

    PubMed

    Gémes, Katalin; Mellidou, Ιfigeneia; Karamanoli, Katerina; Beris, Despoina; Park, Ky Young; Matsi, Theodora; Haralampidis, Kosmas; Constantinidou, Helen-Isis; Roubelakis-Angelakis, Kalliopi A

    2017-04-01

    Polyamine (PA) homeostasis is associated with plant development, growth and responses to biotic/abiotic stresses. Apoplastic PA oxidase (PAO) catalyzes the oxidation of PAs contributing to cellular homeostasis of reactive oxygen species (ROS) and PAs. In tobacco, PAs decrease with plant age, while apoplastic PAO activity increases. Our previous results with young transgenic tobacco plants with enhanced/reduced apoplastic PAO activity (S-ZmPAO/AS-ZmPAO, respectively) established the importance of apoplastic PAO in controlling tolerance to short-term salt stress. However, it remains unclear if the apoplastic PAO pathway is important for salt tolerance at later stages of plant development. In this work, we examined whether apoplastic PAO controls also plant development and tolerance of adult plants during long-term salt stress. The AS-ZmPAO plants contained higher Ca(2+) during salt stress, showing also reduced chlorophyll content index (CCI), leaf area and biomass but taller phenotype compared to the wild-type plants during salt. On the contrary, the S-ZmPAO had more leaves with slightly greater size compared to the AS-ZmPAO and higher antioxidant genes/enzyme activities. Accumulation of proline in the roots was evident at prolonged stress and correlated negatively with PAO deregulation as did the transcripts of genes mediating ethylene biosynthesis. In contrast to the strong effect of apoplastic PAO to salt tolerance in young plants described previously, the effect it exerts at later stages of development is rather moderate. However, the different phenotypes observed in plants deregulating PAO reinforce the view that apoplastic PAO exerts multifaceted roles on plant growth and stress responses. Our data suggest that deregulation of the apoplastic PAO can be further examined as a potential approach to breed plants with enhanced/reduced tolerance to abiotic stress with minimal associated trade-offs.

  10. Policy and research on health manpower regulation: never too late to deregulate?

    PubMed

    Begun, J W; Feldman, R

    1990-01-01

    Research on health manpower regulation has reached a consistent conclusion for the last two decades that is likely to carry into the 1990s: deregulate. Research has progressed in recent years, however, and research in the 1990s will be quite different from that of the past two decades. While the battle cry "never too late to deregulate" will continue to be heard, the "easy" targets, those markets with the least extensive or least important information asymmetry, have already been attacked. What is (or should be) finally emerging in the 1990s is a more challenging appraisal of health manpower regulation, one that recognizes greater complexity in health care markets and consumer preferences than has been recognized in past research. Lessons for the 1990s include the need to recognize, accept, and study information asymmetry and its consequences, and to more closely analyze the hypothesis that occupational interest groups, while meeting their self-interest, also may be serving the commonwealth. Such a reorientation leads us to ask different questions of regulation in future research, all directing attention to the informational attributes of markets: (1) How much information asymmetry exists in different health care markets, and how important is it? In which information-asymmetric markets is manpower regulation most likely to benefit consumers? (2) How can information asymmetry between consumers and providers be reduced, thereby facilitating deregulation? (3) How many regulations, of what type, are consumers willing to eliminate, for what benefits? Simplistic policy recommendations are less likely with this new orientation, and there is a great deal of interesting research awaiting health services researchers.

  11. Implications of deregulation in natural gas industry on utility risks and returns

    NASA Astrophysics Data System (ADS)

    Addepalli, Rajendra P.

    This thesis examines the changes in risk and required return on capital for local distribution utility companies in the increasingly competitive natural gas industry. The deregulation in the industry impacts the LDCs in several ways. First, with the introduction of competition consumers have been given choices among suppliers besides the traditional monopoly, the local utility, for purchasing their natural gas supply needs. Second, with the introduction of competition, some of the interstate pipelines were stuck with 'Take Or Pay' contracts and other costs that resulted in 'stranded costs', which have been passed on to customers of the pipeline including the LDCs. Third, the new obligation for the LDCs to purchase gas from the market, as opposed to buying it from pipelines and passing on the costs to its customers, brought opportunities and risks as well. Finally, with the introduction of competition, in some states LDCs have been allowed to enter into unregulated ventures to increase their profits. In the thesis we first develop a multifactor model (MFM) to explain historical common stock returns of individual utilities and of utility portfolios. We use 'rolling regression' analysis to analyze how different variables explain the variation in stock returns over time. Second, we conduct event studies to analyze the events in the deregulation process that had significant impacts on the LDC returns. Finally we assess the changes in risk and required return on capital for the LDCs over a 15 year time frame, covering the deregulation period. We employ four aspects in the examination of risk and return profile of the utilities: measuring (a) changes in required return on common equity and Weighted Average Cost of Capital, (b) changes in risk premium (WACC less an interest rate proxy), (c) changes in utility bond ratings, and (d) changes in dividend payments, new debt and equity issuances. We perform regression analysis to explain the changes in the required WACC using

  12. Deregulation of Adenosine Receptors in Psoriatic Epidermis: An Option for Therapeutic Treatment.

    PubMed

    Merighi, Stefania; Borea, Pier Andrea; Varani, Katia; Gessi, Stefania

    2017-01-01

    Purinergic signaling is involved in psoriasis, a chronic skin disease characterized by increased epidermis cell growth. In particular, Andrés et al. focus on the keratinocyte biology modulated by adenosine receptors providing evidence that the A2B subtype plays a prominent role in the reduction of keratinocyte proliferation whereas A2A and A2B agonists have antiinflammatory effects independent of adenosine receptors. The authors report that psoriatic epidermis presents a deregulated adenosine receptor expression profile with reduced A2B and increased A2A.

  13. Deregulation of F-box proteins and its consequence on cancer development, progression and metastasis.

    PubMed

    Heo, Jinho; Eki, Rebeka; Abbas, Tarek

    2016-02-01

    F-box proteins are substrate receptors of the SCF (SKP1-Cullin 1-F-box protein) E3 ubiquitin ligase that play important roles in a number of physiological processes and activities. Through their ability to assemble distinct E3 ubiquitin ligases and target key regulators of cellular activities for ubiquitylation and degradation, this versatile group of proteins is able to regulate the abundance of cellular proteins whose deregulated expression or activity contributes to disease. In this review, we describe the important roles of select F-box proteins in regulating cellular activities, the perturbation of which contributes to the initiation and progression of a number of human malignancies.

  14. p27: a barometer of signaling deregulation and potential predictor of response to targeted therapies.

    PubMed

    Wander, Seth A; Zhao, Dekuang; Slingerland, Joyce M

    2011-01-01

    Phosphorylation of the cyclin-dependent kinase inhibitor p27 by upstream mitogenic signaling pathways regulates its stability, localization, and biological function. In human cancers, loss of the antiproliferative action of p27 can arise through reduced protein levels and/or cytoplasmic mislocalization, leading to increased cell proliferation and/or cell migration, respectively. Reduced p27 expression levels and p27 mislocalization have potential prognostic and therapeutic implications in various types of human cancers. This review highlights mechanisms of functional deregulation of p27 by oncogenic signaling that provide an important molecular rationale for pathway targeting in cancer treatment.

  15. MicroRNA deregulation in cancer cells and the tumor microenvironment

    PubMed Central

    Rupaimoole, Rajesha; Calin, George A.; Lopez-Berestein, Gabriel; Sood, Anil K.

    2015-01-01

    MicroRNAs (miRNAs) are a key component of the noncoding RNA family. The underlying mechanisms involved in the interplay between the tumor microenvironment and cancer cells involve highly dynamic factors such as hypoxia and cell types such as cancer-associated fibroblasts and macrophages. Although miRNA levels are known to be altered in cancer cells, recent evidence suggests a critical role for the tumor microenvironment in regulating miRNA biogenesis, methylation, and transcriptional changes. Here, we discuss the complex pro-tumorigenic symbiotic role between tumor cells, the tumor microenvironment, and miRNA deregulation. PMID:26865249

  16. Understanding the Federal Courts.

    ERIC Educational Resources Information Center

    Administrative Office of the United States Courts, Washington, DC.

    This booklet discusses the workings of the federal courts and supports six law-related lesson plans. It is divided into the following sections: "The Constitution and the Federal Judiciary"; "The Federal Courts in American Government" ("The Federal Courts and Congress"; "The Federal Courts and the Executive…

  17. CpaA a novel protease from Acinetobacter baumannii clinical isolates deregulates blood coagulation.

    PubMed

    Tilley, Derek; Law, Robert; Warren, Sarah; Samis, John A; Kumar, Ayush

    2014-07-01

    Acinetobacter baumannii is an important nosocomial pathogen that displays high antibiotic resistance. It causes a variety of infections including pneumonias and sepsis which may result in disseminated intravascular coagulation. In this work, we identify and characterize a novel secreted, zinc-dependent, metallo-endopeptidase CpaA (coagulation targeting metallo-endopeptidase of Acinetobacter baumannii) which deregulates human blood coagulation in vitro and thus is likely to contribute to A. baumannii virulence. Three quarters of the clinical isolates tested (n = 16) had the cpaA gene; however, it was absent from two type strains, A. baumannii ATCC 17978 and A. baumannii ATCC 19606. The CpaA protein was purified from one clinical isolate and was able to cleave purified factor (F) V and fibrinogen and reduce the coagulation activity of FV in human plasma. CpaA-treated plasma showed reduced clotting activity in contact pathway-activated partial thromboplastin time (aPTT) assays, but increased clotting activity in tissue factor pathway prothrombin time (PT) assays. A significant portion of clinically relevant A. baumannii isolates secrete a protease which targets and deregulates the coagulation system.

  18. HTLV-1 Tax deregulates autophagy by recruiting autophagic molecules into lipid raft microdomains.

    PubMed

    Ren, T; Takahashi, Y; Liu, X; Loughran, T P; Sun, S-C; Wang, H-G; Cheng, H

    2015-01-15

    The retroviral oncoprotein Tax from human T-cell leukemia virus type 1 (HTLV-1), an etiological factor that causes adult T-cell leukemia and lymphoma, has a crucial role in initiating T-lymphocyte transformation by inducing oncogenic signaling activation. We here report that Tax is a determining factor for dysregulation of autophagy in HTLV-1-transformed T cells and Tax-immortalized CD4 memory T cells. Tax facilitated autophagic process by activating inhibitor of κB (IκB) kinase (IKK) complex, which subsequently recruited an autophagy molecular complex containing Beclin1 and Bif-1 to the lipid raft microdomains. Tax engaged a crosstalk between IKK complex and autophagic molecule complex by directly interacting with both complexes, promoting assembly of LC3+ autophagosomes. Moreover, expression of lipid raft-targeted Bif-1 or Beclin1 was sufficient to induce formation of LC3+ autophagosomes, suggesting that Tax recruitment of autophagic molecules to lipid rafts is a dominant strategy to deregulate autophagy in the context of HTLV-1 transformation of T cells. Furthermore, depletion of autophagy molecules such as Beclin1 and PI3 kinase class III resulted in impaired growth of HTLV-1-transformed T cells, indicating a critical role of Tax-deregulated autophagy in promoting survival and transformation of virally infected T cells.

  19. Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells.

    PubMed

    Brieño-Enríquez, Miguel A; García-López, Jesús; Cárdenas, David B; Guibert, Sylvain; Cleroux, Elouan; Děd, Lukas; Hourcade, Juan de Dios; Pěknicová, Jana; Weber, Michael; Del Mazo, Jesús

    2015-01-01

    In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs) during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation.

  20. Transcriptome Analysis of Recurrently Deregulated Genes across Multiple Cancers Identifies New Pan-Cancer Biomarkers.

    PubMed

    Kaczkowski, Bogumil; Tanaka, Yuji; Kawaji, Hideya; Sandelin, Albin; Andersson, Robin; Itoh, Masayoshi; Lassmann, Timo; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R

    2016-01-15

    Genes that are commonly deregulated in cancer are clinically attractive as candidate pan-diagnostic markers and therapeutic targets. To globally identify such targets, we compared Cap Analysis of Gene Expression profiles from 225 different cancer cell lines and 339 corresponding primary cell samples to identify transcripts that are deregulated recurrently in a broad range of cancer types. Comparing RNA-seq data from 4,055 tumors and 563 normal tissues profiled in the The Cancer Genome Atlas and FANTOM5 datasets, we identified a core transcript set with theranostic potential. Our analyses also revealed enhancer RNAs, which are upregulated in cancer, defining promoters that overlap with repetitive elements (especially SINE/Alu and LTR/ERV1 elements) that are often upregulated in cancer. Lastly, we documented for the first time upregulation of multiple copies of the REP522 interspersed repeat in cancer. Overall, our genome-wide expression profiling approach identified a comprehensive set of candidate biomarkers with pan-cancer potential, and extended the perspective and pathogenic significance of repetitive elements that are frequently activated during cancer progression.

  1. N-Myc overexpression increases cisplatin resistance in neuroblastoma via deregulation of mitochondrial dynamics

    PubMed Central

    Casinelli, Gabriella; LaRosa, Jeff; Sharma, Manika; Cherok, Edward; Banerjee, Swati; Branca, Maria; Edmunds, Lia; Wang, Yudong; Sims-Lucas, Sunder; Churley, Luke; Kelly, Samantha; Sun, Ming; Stolz, Donna; Graves, J Anthony

    2016-01-01

    N-Myc is a global transcription factor that regulates the expression of genes involved in a number of essential cellular processes including: ribosome biogenesis, cell cycle and apoptosis. Upon deregulation, N-Myc can drive pathologic expression of many of these genes, which ultimately defines its oncogenic potential. Overexpression of N-Myc has been demonstrated to contribute to tumorigenesis, most notably for the pediatric tumor, neuroblastoma. Herein, we provide evidence that deregulated N-Myc alters the expression of proteins involved in mitochondrial dynamics. We found that N-Myc overexpression leads to increased fusion of the mitochondrial reticulum secondary to changes in protein expression due to aberrant transcriptional and post-translational regulation. We believe the structural changes in the mitochondrial network in response to N-Myc amplification in neuroblastoma contributes to two important aspects of tumor development and maintenance—bioenergetic alterations and apoptotic resistance. Specifically, we found that N-Myc overexpressing cells are resistant to programmed cell death in response to exposure to low doses of cisplatin, and demonstrated that this was dependent on increased mitochondrial fusion. We speculate that these changes in mitochondrial structure and function may contribute significantly to the aggressive clinical ph9enotype of N-Myc amplified neuroblastoma. PMID:28028439

  2. Deregulation of the miRNAs Expression in Cervical Cancer: Human Papillomavirus Implications

    PubMed Central

    Gómez-Gómez, Yazmín; Organista-Nava, Jorge; Gariglio, Patricio

    2013-01-01

    MicroRNAs (miRNAs) are a class of small non coding RNAs of 18–25 nucleotides in length. The temporal or short-lived expression of the miRNAs modulates gene expression post transcriptionally. Studies have revealed that miRNAs deregulation correlates and is involved with the initiation and progression of human tumors. Cervical cancer (CC) displays notably increased or decreased expression of a large number of cellular oncogenic or tumor suppressive miRNAs, respectively. However, understanding the potential role of miRNAs in CC is still limited. In CC, the high-risk human papillomaviruses (HR-HPVs) infection can affect the miRNAs expression through oncoprotein E6 and E7 that contribute to viral pathogenesis, although other viral proteins might also be involved. This deregulation in the miRNAs expression has an important role in the hallmarks of CC. Interestingly, the miRNA expression profile in CC can discriminate between normal and tumor tissue and the extraordinary stability of miRNAs makes it suitable to serve as diagnostic and prognostic biomarkers of cancer. In this review, we will summarize the role of the HR-HPVs in miRNA expression, the role of miRNAs in the hallmarks of CC, and the use of miRNAs as potential prognostic biomarkers in CC. PMID:24490161

  3. BPA-Induced Deregulation Of Epigenetic Patterns: Effects On Female Zebrafish Reproduction.

    PubMed

    Santangeli, Stefania; Maradonna, Francesca; Gioacchini, Giorgia; Cobellis, Gilda; Piccinetti, Chiara Carla; Dalla Valle, Luisa; Carnevali, Oliana

    2016-02-25

    Bisphenol A (BPA) is one of the commonest Endocrine Disruptor Compounds worldwide. It interferes with vertebrate reproduction, possibly by inducing deregulation of epigenetic mechanisms. To determine its effects on female reproductive physiology and investigate whether changes in the expression levels of genes related to reproduction are caused by histone modifications, BPA concentrations consistent with environmental exposure were administered to zebrafish for three weeks. Effects on oocyte growth and maturation, autophagy and apoptosis processes, histone modifications, and DNA methylation were assessed by Real-Time PCR (qPCR), histology, and chromatin immunoprecipitation combined with qPCR analysis (ChIP-qPCR). The results showed that 5 μg/L BPA down-regulated oocyte maturation-promoting signals, likely through changes in the chromatin structure mediated by histone modifications, and promoted apoptosis in mature follicles. These data indicate that the negative effects of BPA on the female reproductive system may be due to its upstream ability to deregulate epigenetic mechanism.

  4. BPA-Induced Deregulation Of Epigenetic Patterns: Effects On Female Zebrafish Reproduction

    PubMed Central

    Santangeli, Stefania; Maradonna, Francesca; Gioacchini, Giorgia; Cobellis, Gilda; Piccinetti, Chiara Carla; Dalla Valle, Luisa; Carnevali, Oliana

    2016-01-01

    Bisphenol A (BPA) is one of the commonest Endocrine Disruptor Compounds worldwide. It interferes with vertebrate reproduction, possibly by inducing deregulation of epigenetic mechanisms. To determine its effects on female reproductive physiology and investigate whether changes in the expression levels of genes related to reproduction are caused by histone modifications, BPA concentrations consistent with environmental exposure were administered to zebrafish for three weeks. Effects on oocyte growth and maturation, autophagy and apoptosis processes, histone modifications, and DNA methylation were assessed by Real-Time PCR (qPCR), histology, and chromatin immunoprecipitation combined with qPCR analysis (ChIP-qPCR). The results showed that 5 μg/L BPA down-regulated oocyte maturation-promoting signals, likely through changes in the chromatin structure mediated by histone modifications, and promoted apoptosis in mature follicles. These data indicate that the negative effects of BPA on the female reproductive system may be due to its upstream ability to deregulate epigenetic mechanism. PMID:26911650

  5. And deregulation shall lead me to lie down in green pastures

    SciTech Connect

    Weidinger, G.

    1995-06-01

    This presentation briefly reviews the history of the IPP industry, the current state of competition, and potential opportunities for IPPs in a deregulated environment. Since the beginning of the PURPA created IPP industry, we have experienced many market phases. These began with {open_quotes}beat avoided cost,{close_quotes} followed by {open_quotes}find a need and fill it,{close_quotes} followed by {open_quotes}the bid fest,{close_quotes} to today`s {open_quotes}anything goes.{close_quotes} During this time, market clearing prices have declined from over 80/KwHr to 2-40/KwHr. Today`s partially deregulated electric market includes fierce competition and several new players in the game. Where surplus capacity exists, IPPs must compete with subsidized power. Long-term contracts are no longer widely available. Access to markets is constrained by less than open transmission. Even with these challenges, opportunities remain for the IPP supplier. Opportunities for advanced coal-fired power systems will be explored.

  6. MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients.

    PubMed

    Zhan, Huichun; Cardozo, Christopher; Yu, Wayne; Wang, Antai; Moliterno, Alison R; Dang, Chi V; Spivak, Jerry L

    2013-03-01

    Polycythemia vera (PV) and essential thrombocythemia (ET) are the two most common myeloproliferative neoplasms. The same JAK2(V617F) mutation can be found in both disorders and is able to recapitulate many of the phenotypic abnormalities of these diseases in the murine models. The disease phenotype is also influenced by other unknown genetic or epigenetic factors. MicroRNAs (miRNA) are 18-24 nucleotides single-stranded non-protein-coding RNAs that function primarily as gene repressors by binding to their target messenger RNAs. We performed miRNA expression profiling by oligonucleotide microarray analysis in purified peripheral blood CD34+ cells from eight JAK2(V617F)-positive PV patients and six healthy donors. A quantitative reverse-transcription polymerase chain reaction assay was used to verify differential miRNA expression. Since erythrocytosis is the only feature that distinguishes PV from ET, we also compared specific miRNA expression in the nucleated erythroid cells directly descended from the early erythroid progenitor cells of PV and ET patients. Our data indicate that significant miRNA deregulation occurs in PV CD34+ cells and confirm a genetic basis for the gender-specific differences that characterize PV with respect to miRNA. The results of our study also suggest that deregulated miRNAs may represent an important mechanism by which the PV erythrocytosis and ET thrombocytosis phenotypes are determined.

  7. Deregulation of Genes Related to Iron and Mitochondrial Metabolism in Refractory Anemia with Ring Sideroblasts

    PubMed Central

    del Rey, Mónica; Benito, Rocío; Fontanillo, Celia; Campos-Laborie, Francisco J.; Janusz, Kamila; Velasco-Hernández, Talía; Abáigar, María; Hernández, María; Cuello, Rebeca; Borrego, Daniel; Martín-Zanca, Dionisio; De Las Rivas, Javier; Mills, Ken I.; Hernández-Rivas, Jesús M.

    2015-01-01

    The presence of SF3B1 gene mutations is a hallmark of refractory anemia with ring sideroblasts (RARS). However, the mechanisms responsible for iron accumulation that characterize the Myelodysplastic Syndrome with ring sideroblasts (MDS-RS) are not completely understood. In order to gain insight in the molecular basis of MDS-RS, an integrative study of the expression and mutational status of genes related to iron and mitochondrial metabolism was carried out. A total of 231 low-risk MDS patients and 81 controls were studied. Gene expression analysis revealed that iron metabolism and mitochondrial function had the highest number of genes deregulated in RARS patients compared to controls and the refractory cytopenias with unilineage dysplasia (RCUD). Thus mitochondrial transporters SLC25 (SLC25A37 and SLC25A38) and ALAD genes were over-expressed in RARS. Moreover, significant differences were observed between patients with SF3B1 mutations and patients without the mutations. The deregulation of genes involved in iron and mitochondrial metabolism provides new insights in our knowledge of MDS-RS. New variants that could be involved in the pathogenesis of these diseases have been identified. PMID:25955609

  8. Toward the Identification of Two Glycoproteins Involved in the Stomatal Deregulation of Downy Mildew-Infected Grapevine Leaves.

    PubMed

    Guillier, Christelle; Gamm, Magdalena; Lucchi, Géraldine; Truntzer, Caroline; Pecqueur, Delphine; Ducoroy, Patrick; Adrian, Marielle; Héloir, Marie-Claire

    2015-11-01

    Stomata remain abnormally opened and unresponsive to abscisic acid in grapevine leaves infected by downy mildew. This deregulation occurs from 3 days postinoculation and increases concomitantly with leaf colonization by the pathogen. Using epidermal peels, we demonstrated that the active compound involved in this deregulation is located in the apoplast. Biochemical assays showed that the active compound present in the apoplastic fluids isolated from Plasmopara viticola-infected grapevine leaves (IAF) is a CysCys bridge-independent, thermostable and glycosylated protein. Fractionation guided assays based on chromatography coupled to stomatal response and proteomic analysis allowed the identification of both plant and pathogen proteins in the active fraction obtained from IAF. Further in silico analysis and discriminant filtrations based on the comparison between predictions and experimental indications lead to the identification of two Vitis vinifera proteins as candidates for the observed stomatal deregulation.

  9. The impact of deregulation and restructuring: An empirical case study of the electric utility industry from 1998 through 2007

    NASA Astrophysics Data System (ADS)

    Robinson, Deborah E.

    This qualitative study analyzed the residential electricity prices in the competitive U.S. electric market from 1998 to 2007. This analysis revealed that electricity restructuring has not yet resulted in lower prices for the majority of residential consumers in areas open to competition. This study reviewed actual experiences of eight states in the deregulated and restructured electricity markets: Illinois, Maine, Massachusetts, New Hampshire, Nevada, Pennsylvania, Rhode Island, and Virginia. The study began with a historical look at the deregulated and restructured electricity market from 1990 to 2007. The electricity market was deregulated to include retail competition and price caps. The results indicated that both had an effect on residential prices. This study used data from the Energy Information Administration and the 8 public utility commissions. Contrary to common expectations, residential electricity costs for consumers have increased rather than decreased.

  10. Phenotypic impact of deregulated expression of class I histone deacetylases in urothelial cell carcinoma of the bladder.

    PubMed

    Junqueira-Neto, Susana; Vieira, Filipa Q; Montezuma, Diana; Costa, Natália R; Antunes, Luís; Baptista, Tiago; Oliveira, Ana Isabel; Graça, Inês; Rodrigues, Ângelo; Magalhães, José S; Oliveira, Jorge; Henrique, Rui; Jerónimo, Carmen

    2015-07-01

    Deregulated expression of histone deacetylases (HDACs) has been implicated in tumorigenesis. Herein, we investigated class I HDACs expression in bladder urothelial cell carcinoma (BUCC), its prognostic value and biological significance. Significantly increased transcript levels of all HDACs were found in BUCC compared to 20 normal mucosas, and these were higher in lower grade and stage tumors. Increased HDAC3 levels were associated with improved patient survival. SiRNA experiments showed decrease cell viability and motility, and increased apoptosis. We concluded that class I HDACs play an important role in bladder carcinogenesis through deregulation of proliferation, migration and apoptosis, constituting putative therapeutic targets.

  11. Federal Student Loan Programs

    ERIC Educational Resources Information Center

    Federal Student Aid, US Department of Education, 2014

    2014-01-01

    For those needing a loan to attend college, think federal aid first. Federal student loans usually offer borrowers lower interest rates and have more flexible repayment terms and options than private student loans. This brief report answers the following questions about federal aid: (1) What is a federal student loan?; (2) What is a private…

  12. Allocation of Transaction Cost to Market Participants Using an Analytical Method in Deregulated Market

    NASA Astrophysics Data System (ADS)

    Jeyasankari, S.; Jeslin Drusila Nesamalar, J.; Charles Raja, S.; Venkatesh, P.

    2014-04-01

    Transmission cost allocation is one of the major challenges in transmission open access faced by the electric power sector. The purpose of this work is to provide an analytical method for allocating transmission transaction cost in deregulated market. This research work provides a usage based transaction cost allocation method based on line-flow impact factor (LIF) which relates the power flow in each line with respect to transacted power for the given transaction. This method provides the impact of line flows without running iterative power flow solution and is well suited for real time applications. The proposed method is compared with the Newton-Raphson (NR) method of cost allocation on sample six bus and practical Indian utility 69 bus systems by considering multilateral transaction.

  13. Cell cycle-regulatory cyclins and their deregulation in oral cancer.

    PubMed

    Mishra, Rajakishore

    2013-06-01

    Oral cancer is a growth-related disorder, and cyclins are the prime regulators of cell division. Cyclins are associated with the pathogenesis of oral cancer and are considered valuable biomarkers for diagnosis and prognosis. These important molecules are regulated in many ways to achieve a gain in function and are involved in promoting neoplastic growth. While the causes of most cyclin overexpression are varied, these cyclins may be induced by buccal mucosal insult mainly with carcinogens that alter various pathways propelling oral cancer. Substantial experimental evidences support a link between oncogenic signaling pathways and the deregulation of cyclins in oral cancer. This review focuses on the mechanisms by which cyclins are regulated and promote oral oncogenesis.

  14. A deregulated intestinal cell cycle program disrupts tissue homeostasis without affecting longevity in Drosophila.

    PubMed

    Petkau, Kristina; Parsons, Brendon D; Duggal, Aashna; Foley, Edan

    2014-10-10

    Recent studies illuminate a complex relationship between the control of stem cell division and intestinal tissue organization in the model system Drosophila melanogaster. Host and microbial signals drive intestinal proliferation to maintain an effective epithelial barrier. Although it is widely assumed that proliferation induces dysplasia and shortens the life span of the host, the phenotypic consequences of deregulated intestinal proliferation for an otherwise healthy host remain unexplored. To address this question, we genetically isolated and manipulated the cell cycle programs of adult stem cells and enterocytes. Our studies revealed that cell cycle alterations led to extensive cell death and morphological disruptions. Despite the extensive tissue damage, we did not observe an impact on longevity, suggesting a remarkable degree of plasticity in intestinal function.

  15. The role of clean coal technologies in a deregulated rural utility market

    SciTech Connect

    Neal, J.W.

    1997-12-31

    The nation`s rural electric cooperatives own a high proportion of coal-fired generation, in excess of 80 percent of their generating capacity. As the electric utility industry moves toward a competitive electricity market, the generation mix for electric cooperatives is expected to change. Distributed generation will likely serve more customer loads than is now the case, and that will lead to an increase in gas-fired generation capacity. But, clean low-cost central station coal-fired capacity is expected to continue to be the primary source of power for growing rural electric cooperatives. Gasification combined cycle could be the lowest cost coal based generation option in this new competitive market if both capital cost and electricity production costs can be further reduced. This paper presents anticipated utility business scenarios for the deregulated future and identifies combined cycle power plant configurations that might prove most competitive.

  16. CCT`s in a deregulated environment: A producer`s perspective

    SciTech Connect

    Edmonds, R.F. Jr.; Fayssoux, J.O.

    1997-12-31

    The US electric industry will be deregulated (or substantially re-regulated) within 5 years. Several states, including California, Rhode Island, and New Hampshire, already have passed legislation to introduce competition into the electric markets before the year 2000. As this trend sweeps across the country, the resulting competitive market for generation will reward the lowest cost producers and force high cost producers out of the market. As a result, at least in the short run, it may be very difficult for new power plants employing Clean Coal Technologies (CCTs) to compete. This paper discusses a producer`s perspective of the new competitive market, and suggests several short and long term strategies and niches for CCTs.

  17. Deregulated MicroRNAs in Biliary Tract Cancer: Functional Targets and Potential Biomarkers

    PubMed Central

    Beyreis, Marlena; Wagner, Andrej; Pichler, Martin; Neureiter, Daniel

    2016-01-01

    Biliary tract cancer (BTC) is still a fatal disease with very poor prognosis. The lack of reliable biomarkers for early diagnosis and of effective therapeutic targets is a major demanding problem in diagnosis and management of BTC. Due to the clinically silent and asymptomatic characteristics of the tumor, most patients are diagnosed at an already advanced stage allowing only for a palliative therapeutic approach. MicroRNAs are small noncoding RNAs well known to regulate various cellular functions and pathologic events including the formation and progression of cancer. Over the last years, several studies have shed light on the role of microRNAs in BTC, making them potentially attractive therapeutic targets and candidates as biomarkers. In this review, we will focus on the role of oncogenic and tumor suppressor microRNAs and their direct targets in BTC. Furthermore, we summarize and discuss data that evaluate the diagnostic power of deregulated microRNAs as possible future biomarkers for BTC. PMID:27957497

  18. Deregulation of protein translation control, a potential game-changing hypothesis for Parkinson's disease pathogenesis.

    PubMed

    Taymans, Jean-Marc; Nkiliza, Aurore; Chartier-Harlin, Marie-Christine

    2015-08-01

    Protein translation is one of the most fundamental and exquisitely controlled processes in biology, and is energetically demanding. The deregulation of this process is deleterious to cells, as demonstrated by several diseases caused by mutations in protein translation machinery. Emerging evidence now points to a role for protein translation in the pathogenesis of Parkinson's disease (PD); a debilitating neurodegenerative movement disorder. In this paper, we propose a hypothesis that protein translation machinery, PD-associated proteins and PD pathology are connected in a functional network linking cell survival to protein translation control. This hypothesis is a potential game changer in the field of the molecular pathogenesis of PD, with implications for the development of PD diagnostics and disease-modifying therapies.

  19. IODNE: An integrated optimization method for identifying the deregulated subnetwork for precision medicine in cancer

    PubMed Central

    Mounika Inavolu, S; Renbarger, J; Radovich, M; Vasudevaraja, V; Kinnebrew, GH; Zhang, S

    2017-01-01

    Subnetwork analysis can explore complex patterns of entire molecular pathways for the purpose of drug target identification. In this article, the gene expression profiles of a cohort of patients with breast cancer are integrated with protein‐protein interaction (PPI) networks using, simultaneously, both edge scoring and node scoring. A novel optimization algorithm, integrated optimization method to identify deregulated subnetwork (IODNE), is developed to search for the optimal dysregulated subnetwork of the merged gene and protein network. IODNE is applied to select subnetworks for Luminal‐A breast cancer from The Cancer Genome Atlas (TCGA) data. A large fraction of cancer‐related genes and the well‐known clinical targets, ER1/PR and HER2, are found by IODNE. This validates the utility of IODNE. When applying IODNE to the triple‐negative breast cancer (TNBC) subtype data, we identified subnetworks that contain genes such as ERBB2, HRAS, PGR, CAD, POLE, and SLC2A1. PMID:28266149

  20. Deregulation of intestinal anti-microbial defense by the dietary additive, maltodextrin.

    PubMed

    Nickerson, Kourtney P; Chanin, Rachael; McDonald, Christine

    2015-01-01

    Inflammatory bowel disease (IBD) is a complex, multi-factorial disease thought to arise from an inappropriate immune response to commensal bacteria in a genetically susceptible person that results in chronic, cyclical, intestinal inflammation. Dietary and environmental factors are implicated in the initiation and perpetuation of IBD; however, a singular causative agent has not been identified. As of now, the role of environmental priming or triggers in IBD onset and pathogenesis are not well understood, but these factors appear to synergize with other disease susceptibility factors. In previous work, we determined that the polysaccharide dietary additive, maltodextrin (MDX), impairs cellular anti-bacterial responses and suppresses intestinal anti-microbial defense mechanisms. In this addendum, we review potential mechanisms for dietary deregulation of intestinal homeostasis, postulate how dietary and genetic risk factors may combine to result in disease pathogenesis, and discuss these ideas in the context of recent findings related to dietary interventions for IBD.

  1. Aberrantly Expressed OTX Homeobox Genes Deregulate B-Cell Differentiation in Hodgkin Lymphoma

    PubMed Central

    Nagel, Stefan; Ehrentraut, Stefan; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G.; MacLeod, Roderick A. F.

    2015-01-01

    In Hodgkin lymphoma (HL) we recently reported that deregulated homeobox gene MSX1 mediates repression of the B-cell specific transcription factor ZHX2. In this study we investigated regulation of MSX1 in this B-cell malignancy. Accordingly, we analyzed expression and function of OTX homeobox genes which activate MSX1 transcription during embryonal development in the neural plate border region. Our data demonstrate that OTX1 and OTX2 are aberrantly expressed in both HL patients and cell lines. Moreover, both OTX loci are targeted by genomic gains in overexpressing cell lines. Comparative expression profiling and subsequent pathway modulations in HL cell lines indicated that aberrantly enhanced FGF2-signalling activates the expression of OTX2. Downstream analyses of OTX2 demonstrated transcriptional activation of genes encoding transcription factors MSX1, FOXC1 and ZHX1. Interestingly, examination of the physiological expression profile of ZHX1 in normal hematopoietic cells revealed elevated levels in T-cells and reduced expression in B-cells, indicating a discriminatory role in lymphopoiesis. Furthermore, two OTX-negative HL cell lines overexpressed ZHX1 in correlation with genomic amplification of its locus at chromosomal band 8q24, supporting the oncogenic potential of this gene in HL. Taken together, our data demonstrate that deregulated homeobox genes MSX1 and OTX2 respectively impact transcriptional inhibition of (B-cell specific) ZHX2 and activation of (T-cell specific) ZHX1. Thus, we show how reactivation of a specific embryonal gene regulatory network promotes disturbed B-cell differentiation in HL. PMID:26406991

  2. Regulation and deregulation of cholesterol homeostasis: The liver as a metabolic “power station”

    PubMed Central

    Trapani, Laura; Segatto, Marco; Pallottini, Valentina

    2012-01-01

    Cholesterol plays several structural and metabolic roles that are vital for human biology. It spreads along the entire plasma membrane of the cell, modulating fluidity and concentrating in specialized sphingolipid-rich domains called rafts and caveolae. Cholesterol is also a substrate for steroid hormones. However, too much cholesterol can lead to pathological pictures such as atherosclerosis, which is a consequence of the accumulation of cholesterol into the cells of the artery wall. The liver is considered to be the metabolic power station of mammalians, where cholesterol homeostasis relies on an intricate network of cellular processes whose deregulations can lead to several life-threatening pathologies, such as familial and age-related hypercholesterolemia. Cholesterol homeostasis maintenance is carried out by: biosynthesis, via 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity; uptake, through low density lipoprotein receptors (LDLr); lipoprotein release in the blood; storage by esterification; and degradation and conversion into bile acids. Both HMGR and LDLr are transcribed as a function of cellular sterol amount by a family of transcription factors called sterol regulatory element binding proteins that are responsible for the maintenance of cholesterol homeostasis through an intricate mechanism of regulation. Cholesterol obtained by hepatic de novo synthesis can be esterified and incorporated into apolipoprotein B-100-containing very low density lipoproteins, which are then secreted into the bloodstream for transport to peripheral tissues. Moreover, dietary cholesterol is transferred from the intestine to the liver by high density lipoproteins (HDLs); all HDL particles are internalized in the liver, interacting with the hepatic scavenger receptor (SR-B1). Here we provide an updated overview of liver cholesterol metabolism regulation and deregulation and the causes of cholesterol metabolism-related diseases. Moreover, current pharmacological

  3. Regulation and deregulation of cholesterol homeostasis: The liver as a metabolic "power station".

    PubMed

    Trapani, Laura; Segatto, Marco; Pallottini, Valentina

    2012-06-27

    Cholesterol plays several structural and metabolic roles that are vital for human biology. It spreads along the entire plasma membrane of the cell, modulating fluidity and concentrating in specialized sphingolipid-rich domains called rafts and caveolae. Cholesterol is also a substrate for steroid hormones. However, too much cholesterol can lead to pathological pictures such as atherosclerosis, which is a consequence of the accumulation of cholesterol into the cells of the artery wall. The liver is considered to be the metabolic power station of mammalians, where cholesterol homeostasis relies on an intricate network of cellular processes whose deregulations can lead to several life-threatening pathologies, such as familial and age-related hypercholesterolemia. Cholesterol homeostasis maintenance is carried out by: biosynthesis, via 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity; uptake, through low density lipoprotein receptors (LDLr); lipoprotein release in the blood; storage by esterification; and degradation and conversion into bile acids. Both HMGR and LDLr are transcribed as a function of cellular sterol amount by a family of transcription factors called sterol regulatory element binding proteins that are responsible for the maintenance of cholesterol homeostasis through an intricate mechanism of regulation. Cholesterol obtained by hepatic de novo synthesis can be esterified and incorporated into apolipoprotein B-100-containing very low density lipoproteins, which are then secreted into the bloodstream for transport to peripheral tissues. Moreover, dietary cholesterol is transferred from the intestine to the liver by high density lipoproteins (HDLs); all HDL particles are internalized in the liver, interacting with the hepatic scavenger receptor (SR-B1). Here we provide an updated overview of liver cholesterol metabolism regulation and deregulation and the causes of cholesterol metabolism-related diseases. Moreover, current pharmacological

  4. Integrated Computing, Communication, and Distributed Control of Deregulated Electric Power Systems

    SciTech Connect

    Bajura, Richard; Feliachi, Ali

    2008-09-24

    Restructuring of the electricity market has affected all aspects of the power industry from generation to transmission, distribution, and consumption. Transmission circuits, in particular, are stressed often exceeding their stability limits because of the difficulty in building new transmission lines due to environmental concerns and financial risk. Deregulation has resulted in the need for tighter control strategies to maintain reliability even in the event of considerable structural changes, such as loss of a large generating unit or a transmission line, and changes in loading conditions due to the continuously varying power consumption. Our research efforts under the DOE EPSCoR Grant focused on Integrated Computing, Communication and Distributed Control of Deregulated Electric Power Systems. This research is applicable to operating and controlling modern electric energy systems. The controls developed by APERC provide for a more efficient, economical, reliable, and secure operation of these systems. Under this program, we developed distributed control algorithms suitable for large-scale geographically dispersed power systems and also economic tools to evaluate their effectiveness and impact on power markets. Progress was made in the development of distributed intelligent control agents for reliable and automated operation of integrated electric power systems. The methodologies employed combine information technology, control and communication, agent technology, and power systems engineering in the development of intelligent control agents for reliable and automated operation of integrated electric power systems. In the event of scheduled load changes or unforeseen disturbances, the power system is expected to minimize the effects and costs of disturbances and to maintain critical infrastructure operational.

  5. Deregulated HOX genes in ameloblastomas are located in physical contiguity to keratin genes.

    PubMed

    Schiavo, Giulia; D'Antò, Vincenzo; Cantile, Monica; Procino, Alfredo; Di Giovanni, Stefano; Valletta, Rossella; Terracciano, Luigi; Baumhoer, Daniel; Jundt, Gernot; Cillo, Clemente

    2011-11-01

    The expression of the HOX gene network in mid-stage human tooth development mostly concerns the epithelial tooth germ compartment and involves the C and D HOX loci. To further dissect the HOX gene implication with tooth epithelium differentiation we compared the expression of the whole HOX network in human ameloblastomas, as paradigm of epithelial odontogenic tumors, with tooth germs. We identified two ameloblastoma molecular types with respectively low and high number of active HOX C genes. The highly expressing HOX C gene ameloblastomas were characterized by a strong keratinized phenotype. Locus C HOX genes are located on chromosome 12q13-15 in physical contiguity with one of the two keratin gene clusters included in the human genome. The most posterior HOX C gene, HOX C13, is capable to interact with hair keratin genes located on the other keratin gene cluster in physical contiguity with the HOX B locus on chromosome 17q21-22. Inside the HOX C locus, a 2.2 kb ncRNA (HOTAIR) able to repress transcription, in cis, along the entire HOX C locus and, in trans, at the posterior region of the HOX D locus has recently been identified. Interestingly both loci are deregulated in ameloblastomas. Our finding support an important role of the HOX network in characterizing the epithelial tooth compartment. Furthermore, the physical contiguity between locus C HOX and keratin genes in normal tooth epithelium and their deregulation in the neoplastic counterparts suggest they may act on the same mechanism potentially involved with epithelial tumorigenesis.

  6. Deregulating School Aid in California: How 10 Districts Responded to Fiscal Flexibility, 2009-2010. Research Report Number 2

    ERIC Educational Resources Information Center

    Fuller, Bruce; Marsh, Julie A.; Stecher, Brian M.; Timar, Tom

    2011-01-01

    In 2009, California state legislators freed local educators from the specific guidelines that previously regulated spending on 40 categorical-aid programs known as Tier 3 programs. This Tier 3 flexibility reform, which deregulates $4.5 billion in education funding, was enacted at the same time the legislature made cuts in education spending in…

  7. 76 FR 5787 - Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-02

    ... Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant Programs... Perkins Loan, Federal Work-Study (FWS), and Federal Supplemental Educational Opportunity Grant (FSEOG... Federal Perkins Loan Program, Federal Work-Study Program, and Federal Supplemental Educational...

  8. TAP Service Federation Factory

    NASA Astrophysics Data System (ADS)

    Hume, A. C.; Krause, A.; Holliman, M.; Mann, R. G.; Noddle, K.; Voutsinas, S.

    2012-09-01

    This paper describes a prototype federation service for multiple TAP endpoints. Users can create a new TAP resource that allows them to query the federation as if all tables were in a single database.

  9. The MAPK1/3 pathway is essential for the deregulation of autophagy observed in G2019S LRRK2 mutant fibroblasts

    PubMed Central

    Bravo-San Pedro, José M.; Gómez-Sánchez, Rubén; Niso-Santano, Mireia; Pizarro-Estrella, Elisa; Aiastui-Pujana, Ana; Gorostidi, Ana; Climent, Vicente; López de Maturana, Rakel; Sanchez-Pernaute, Rosario; López de Munain, Adolfo; Fuentes, José M.; González-Polo, Rosa A.

    2012-01-01

    The link between the deregulation of autophagy and cell death processes can be essential in the development of several neurodegenerative diseases, such as Parkinson disease (PD). However, the molecular mechanism of deregulation of this degradative process in PD patients is unknown. The leucine-rich repeat kinase 2 (LRRK2) gene is related to PD and its implication in autophagy regulation has been described. Our recent work shows that the presence of the G2019S LRRK2 mutation, one of the most prevalent in LRRK2, is accompanied by a deregulation of autophagy basal levels dependent on the MAPK1/3 (ERK2/1) pathway. PMID:22914360

  10. Deregulation of mTOR signaling is involved in thymic lymphoma development in Atm-/- mice

    SciTech Connect

    Kuang, Xianghong; Shen, Jianjun; Wong, Paul K.Y.; Yan, Mingshan

    2009-06-05

    Abnormal thymocyte development with thymic lymphomagenesis inevitably occurs in Atm-/- mice, indicating that ATM plays a pivotal role in regulating postnatal thymocyte development and preventing thymic lymphomagenesis. The mechanism for ATM controls these processes is unclear. We have shown previously that c-Myc, an oncoprotein regulated by the mammalian target of rapamycin (mTOR), is overexpressed in Atm-/- thymocytes. Here, we show that inhibition of mTOR signaling with its specific inhibitor, rapamycin, suppresses normal thymocyte DNA synthesis by downregulating 4EBP1, but not S6K, and that 4EBP1 phosphorylation and cyclin D1 expression are coordinately increased in Atm-/- thymocytes. Administration of rapamycin to Atm-/- mice attenuates elevated phospho-4EBP1, c-Myc and cyclin D1 in their thymocytes, and delays thymic lymphoma development. These results indicate that mTOR downstream effector 4EBP1 is essential for normal thymocyte proliferation, but deregulation of 4EBP1 in Atm deficiency is a major factor driving thymic lymphomagenesis in the animals.

  11. Truncated tau deregulates synaptic markers in rat model for human tauopathy

    PubMed Central

    Jadhav, Santosh; Katina, Stanislav; Kovac, Andrej; Kazmerova, Zuzana; Novak, Michal; Zilka, Norbert

    2015-01-01

    Synaptic failure and neurofibrillary degeneration are two major neuropathological substrates of cognitive dysfunction in Alzheimer’s disease (AD). Only a few studies have demonstrated a direct relationship between these two AD hallmarks. To investigate tau mediated synaptic injury we used rat model of tauopathy that develops extensive neurofibrillary pathology in the cortex. Using fractionation of cortical synapses, we identified an increase in endogenous rat tau isoforms in presynaptic compartment, and their mis-sorting to the postsynaptic density (PSD). Truncated transgenic tau was distributed in both compartments exhibiting specific phospho-pattern that was characteristic for each synaptic compartment. In the presynaptic compartment, truncated tau was associated with impairment of dynamic stability of microtubules which could be responsible for reduction of synaptic vesicles. In the PSD, truncated tau lowered the levels of neurofilaments. Truncated tau also significantly decreased the synaptic levels of Aβ40 but not Aβ42. These data show that truncated tau differentially deregulates synaptic proteome in pre- and postsynaptic compartments. Importantly, we show that alteration of Aβ can arise downstream of truncated tau pathology. PMID:25755633

  12. Deletion of Type I glutamine synthetase deregulates nitrogen metabolism and increases ethanol production in Clostridium thermocellum.

    PubMed

    Rydzak, Thomas; Garcia, David; Stevenson, David M; Sladek, Margaret; Klingeman, Dawn M; Holwerda, Evert K; Amador-Noguez, Daniel; Brown, Steven D; Guss, Adam M

    2017-04-08

    Clostridium thermocellum rapidly deconstructs cellulose and ferments resulting hydrolysis products into ethanol and other products, and is thus a promising platform organism for the development of cellulosic biofuel production via consolidated bioprocessing. While recent metabolic engineering strategies have targeted eliminating canonical fermentation products (acetate, lactate, formate, and H2), C. thermocellum also secretes amino acids, which has limited ethanol yields in engineered strains to approximately 70% of the theoretical maximum. To investigate approaches to decrease amino acid secretion, we attempted to reduce ammonium assimilation by deleting the Type I glutamine synthetase (glnA) in an essentially wild type strain of C. thermocellum. Deletion of glnA reduced levels of secreted valine and total amino acids by 53% and 44% respectively, and increased ethanol yields by 53%. RNA-seq analysis revealed that genes encoding the RNF-complex were more highly expressed in ΔglnA and may have a role in improving NADH-availability for ethanol production. While a significant up-regulation of genes involved in nitrogen assimilation and urea uptake suggested that deletion of glnA induces a nitrogen starvation response, metabolomic analysis showed an increase in intracellular glutamine levels indicative of nitrogen-rich conditions. We propose that deletion of glnA causes deregulation of nitrogen metabolism, leading to overexpression of nitrogen metabolism genes and, in turn, elevated glutamine levels. Here we demonstrate that perturbation of nitrogen assimilation is a promising strategy to redirect flux from the production of nitrogenous compounds toward biofuels in C. thermocellum.

  13. Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression

    PubMed Central

    Russo, Maria Veronica; Gazzano, Giacomo; Giangiobbe, Sara; Montanari, Emanuele; Del Nero, Alberto; Rocco, Bernardo; Albo, Giancarlo; Languino, Lucia R.; Altieri, Dario C.; Vaira, Valentina; Bosari, Silvano

    2015-01-01

    Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the “stemness” marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease. PMID:26107383

  14. Functional analysis reveals that RBM10 mutations contribute to lung adenocarcinoma pathogenesis by deregulating splicing

    PubMed Central

    Zhao, Jiawei; Sun, Yue; Huang, Yin; Song, Fan; Huang, Zengshu; Bao, Yufang; Zuo, Ji; Saffen, David; Shao, Zhen; Liu, Wen; Wang, Yongbo

    2017-01-01

    RBM10 is an RNA splicing regulator that is frequently mutated in lung adenocarcinoma (LUAD) and has recently been proposed to be a cancer gene. How RBM10 mutations observed in LUAD affect its normal functions, however, remains largely unknown. Here integrative analysis of RBM10 mutation and RNA expression data revealed that LUAD-associated RBM10 mutations exhibit a mutational spectrum similar to that of tumor suppressor genes. In addition, this analysis showed that RBM10 mutations identified in LUAD patients lacking canonical oncogenes are associated with significantly reduced RBM10 expression. To systematically investigate RBM10 mutations, we developed an experimental pipeline for elucidating their functional effects. Among six representative LUAD-associated RBM10 mutations, one nonsense and one frameshift mutation caused loss-of-function as expected, whereas four missense mutations differentially affected RBM10-mediated splicing. Importantly, changes in proliferation rates of LUAD-derived cells caused by these RBM10 missense mutants correlated with alterations in RNA splicing of RBM10 target genes. Together, our data implies that RBM10 mutations contribute to LUAD pathogenesis, at least in large part, by deregulating splicing. The methods described in this study should be useful for analyzing mutations in additional cancer-associated RNA splicing regulators. PMID:28091594

  15. Lipid deregulation in UV irradiated skin cells: Role of 25-hydroxycholesterol in keratinocyte differentiation during photoaging.

    PubMed

    Olivier, Elodie; Dutot, Mélody; Regazzetti, Anne; Dargère, Delphine; Auzeil, Nicolas; Laprévote, Olivier; Rat, Patrice

    2016-05-18

    Skin photoaging due to UV irradiation is a degenerative process that appears more and more as a growing concern. Lipids, including oxysterols, are involved in degenerative processes; as skin cells contain various lipids, the aim of our study was to evaluate first, changes in keratinocyte lipid levels induced by UV exposure and second, cellular effects of oxysterols in cell morphology and several hallmarks of keratinocyte differentiation. Our mass spectrometry results demonstrated that UV irradiation induces changes in lipid profile of cultured keratinocytes; in particular, ceramides and oxysterols, specifically 25-hydroxycholesterol (25-OH), were increased. Using holography and confocal microscopy analyses, we highlighted cell thickening and cytoskeletal disruption after incubation of keratinocytes with 25-OH. These alterations were associated with keratinocyte differentiation patterns: autophagy stimulation and intracellular calcium increase as measured by cytofluorometry, and increased involucrin level detected by immunocytochemistry. To conclude, oxysterol deregulation could be considered as a common marker of degenerative disorders. During photoaging, 25-OH seems to play a key role inducing morphological changes and keratinocyte differentiation.

  16. Image is all: Deregulation, restructuring and reputation in the natural gas industry

    SciTech Connect

    1997-09-01

    Does image affect how one views his local utility company--or energy supplier? Does one value his utility companies more if one sees a lot of image advertising and public relations stories about community involvement, environmental action and charitable work? Or does one view utilities as faceless and anonymous entities that provide necessary services one thinks little about until there`s a problem? And, more important, what is the role of utility image in an era of deregulation, as companies begin a new scramble for customers? To find an answer to these questions, American Gas and Christopher Bonner Consultants conducted a survey of A.G.A. member companies to learn what, if anything, utility companies are doing in the areas of image assessment and change. The survey was sent to more than 200 A.G.A. member companies; written responses were received from 35. In addition, 13 follow-up telephone interviews were conducted, including four with companies that had not responded in writing. The picture that emerges if of an industry that is starting to pay greater and greater attention to image. And, as utilities reorganize and redefine themselves, they are also reexamining the ways they communicate with key audiences, including employees, customers, legislators, the financial community and the news media.

  17. Deregulation of paralogous 13 HOX genes in oral squamous cell carcinoma.

    PubMed

    Aquino, Gabriella; Franco, Renato; Sabatino, Rocco; Mantia, Elvira La; Scognamiglio, Giosuè; Collina, Francesca; Longo, Francesco; Ionna, Franco; Losito, Nunzia S; Liguori, Giuseppina; Botti, Gerardo; Cantile, Monica

    2015-01-01

    Many oncogenic drivers related to the pathogenesis of OSCC have identified, but the discovery of new molecular markers for early detection of this cancer, remains one the main goals of clinical research. HOX genes regulate normal embryonic development, cell differentiation and other critical processes in eukaryotic cell life. Several studies have demonstrated that the deregulation of HOX genes play a significant role in cancer development and progression. In this study, we built a prognostic TMA with 119 OSCC samples, representative of deep and superficial part of the tumour, to investigate, the paralogous 13 HOX proteins expression, correlating them with clinicpathological parameters, outcomes and therapy information. Our results show an aberrant expression of HOX A13 and HOX D13 in OSCC pathogenesis and tumour progression. HOX A13 overexpression is related to an OSCC better prognosis (P=0.029) and better therapy response in patients treated with both radiotherapy and chemotherapy (P=0.015). HOX D13 overexpression is inversely related to an overall survival (P=0.004). These data highlight the potential prognostic role of HOX paralogous group 13 genes in OSCC.

  18. Psychosine induces the dephosphorylation of neurofilaments by deregulation of PP1 and PP2A phosphatases

    PubMed Central

    Cantuti-Castelvetri, Ludovico; Zhu, Hongling; Givogri, Maria I.; Chidavaenzi, Robstein L.; Lopez-Rosas, Aurora; Bongarzone, Ernesto R.

    2012-01-01

    Patients with Krabbe disease, a genetic demyelinating syndrome caused by deficiency of galactosyl-ceramidase and the resulting accumulation of galactosyl-sphingolipids, develop signs of a dying-back axonopathy compounded by a deficiency of large-caliber axons. Here, we show that axonal caliber in Twitcher mice, an animal model for Krabbe disease, is impaired in peripheral axons and is accompanied by a progressive reduction in the abundance and phosphorylation of the three neurofilament (NF) subunits. These changes correlate with an increase in the density of NFs per cross-sectional area in numerous mutant peripheral axons and abnormal increases in the activity of two serine/threonine phosphatases (PP1 and PP2A) in mutant tissue. Similarly, acutely isolated mutant cortical neurons show abnormal phosphorylation of NFs. Psychosine, the neurotoxin accumulated in Krabbe disease, was sufficient to induce abnormal dephosphorylation of NF subunits in a normal motor neuron cell line as well as in acutely isolated normal cortical neurons. This in vitro effect was mediated by PP1 and PP2A, which specifically dephosphorylated NFs. These results demonstrate that the reduced caliber observed in some axons in Krabbe disease involves abnormal dephosphorylation of NFs. We propose that a psychosine-driven pathogenic mechanism through deregulated phosphotransferase activities may be involved in this process. PMID:22326830

  19. Direct targeting of Arabidopsis cysteine synthase complexes with synthetic polypeptides to selectively deregulate cysteine synthesis.

    PubMed

    Wawrzyńska, Anna; Kurzyk, Agata; Mierzwińska, Monika; Płochocka, Danuta; Wieczorek, Grzegorz; Sirko, Agnieszka

    2013-06-01

    Biosynthesis of cysteine is one of the fundamental processes in plants providing the reduced sulfur for cell metabolism. It is accomplished by the sequential action of two enzymes, serine acetyltransferase (SAT) and O-acetylserine (thiol) lyase (OAS-TL). Together they constitute the hetero-oligomeric cysteine synthase (CS) complex through specific protein-protein interactions influencing the rate of cysteine production. The aim of our studies was to deregulate the CS complex formation in order to investigate its function in the control of sulfur homeostasis and optimize cysteine synthesis. Computational modeling was used to build a model of the Arabidopsis thaliana mitochondrial CS complex. Several polypeptides based on OAS-TL C amino-acid sequence found at SAT-OASTL interaction sites were designed as probable competitors for SAT3 binding. After verification of the binding in a yeast two-hybrid assay, the most strongly interacting polypeptide was introduced to different cellular compartments of Arabidopsis cell via genetic transformation. Moderate increase in total SAT and OAS-TL activities, but not thiols content, was observed dependent on the transgenic line and sulfur availability in the hydroponic medium. Though our studies demonstrate the proof of principle, they also suggest more complex interaction of both enzymes underlying the mechanism of their reciprocal regulation.

  20. Head lice surveillance on a deregulated OTC-sales market: a study using web query data.

    PubMed

    Lindh, Johan; Magnusson, Måns; Grünewald, Maria; Hulth, Anette

    2012-01-01

    The head louse, Pediculus humanus capitis, is an obligate ectoparasite that causes infestations of humans. Studies have demonstrated a correlation between sales figures for over-the-counter (OTC) treatment products and the number of humans with head lice. The deregulation of the Swedish pharmacy market on July 1, 2009, decreased the possibility to obtain complete sale figures and thereby the possibility to obtain yearly trends of head lice infestations. In the presented study we wanted to investigate whether web queries on head lice can be used as substitute for OTC sales figures. Via Google Insights for Search and Vårdguiden medical web site, the number of queries on "huvudlöss" (head lice) and "hårlöss" (lice in hair) were obtained. The analysis showed that both the Vårdguiden series and the Google series were statistically significant (p<0.001) when added separately, but if the Google series were already included in the model, the Vårdguiden series were not statistically significant (p = 0.5689). In conclusion, web queries can detect if there is an increase or decrease of head lice infested humans in Sweden over a period of years, and be as reliable a proxy as the OTC-sales figures.

  1. CDX2-driven leukemogenesis involves KLF4 repression and deregulated PPARγ signaling

    PubMed Central

    Faber, Katrin; Bullinger, Lars; Ragu, Christine; Garding, Angela; Mertens, Daniel; Miller, Christina; Martin, Daniela; Walcher, Daniel; Döhner, Konstanze; Döhner, Hartmut; Claus, Rainer; Plass, Christoph; Sykes, Stephen M.; Lane, Steven W.; Scholl, Claudia; Fröhling, Stefan

    2012-01-01

    Aberrant expression of the homeodomain transcription factor CDX2 occurs in most cases of acute myeloid leukemia (AML) and promotes leukemogenesis, making CDX2, in principle, an attractive therapeutic target. Conversely, CDX2 acts as a tumor suppressor in colonic epithelium. The effectors mediating the leukemogenic activity of CDX2 and the mechanism underlying its context-dependent properties are poorly characterized, and strategies for interfering with CDX2 function in AML remain elusive. We report data implicating repression of the transcription factor KLF4 as important for the oncogenic activity of CDX2, and demonstrate that CDX2 differentially regulates KLF4 in AML versus colon cancer cells through a mechanism that involves tissue-specific patterns of promoter binding and epigenetic modifications. Furthermore, we identified deregulation of the PPARγ signaling pathway as a feature of CDX2-associated AML and observed that PPARγ agonists derepressed KLF4 and were preferentially toxic to CDX2+ leukemic cells. These data delineate transcriptional programs associated with CDX2 expression in hematopoietic cells, provide insight into the antagonistic duality of CDX2 function in AML versus colon cancer, and suggest reactivation of KLF4 expression, through modulation of PPARγ signaling, as a therapeutic modality in a large proportion of AML patients. PMID:23202735

  2. PKC iota promotes ovarian tumor progression through deregulation of cyclin E

    PubMed Central

    Nanos-Webb, Angela; Bui, Tuyen; Karakas, Cansu; Zhang, Dong; Carey, Jason P.W.; Mills, Gordon B.; Hunt, Kelly K.; Keyomarsi, Khandan

    2016-01-01

    The high frequency of relapse of epithelial ovarian tumors treated with standard chemotherapy has highlighted the necessity to identify targeted therapies that can improve patient outcomes. The dynamic relationship between Cyclin E and PKCiota frequent overexpression in high-grade ovarian tumors poses a novel pathway for therapeutic investigation. We hypothesized that a PI3K dependent signaling pathway activating PKCiota perpetuates cyclin E deregulation during ovarian tumorigenesis. We observed a positive correlation between PKCiota and cyclin E in a panel of 19 ovarian cancer cell lines. Modulation of cyclin E had no effect on PKCiota knockdown/overexpression however PKCiota differentially regulated cyclin E expression. In the serous ovarian cancer cells (IGROV, OVCAR-3), shPKCiota decreased proliferation, caused a G1 arrest, and significantly prolonged overall survival in xenograft mouse models. In vitro shPKCiota decreased the ability of IGROV cells to grow under anchorage independent conditions and form aberrant acini, which was dependent upon Ad-cyclin E or Ad-LMW-E expression. RPPA analysis of PKCiota wild-type, catalytic active, dominant negative protein isoforms strengthened the association between phospho-PKCiota levels and PI3K pathway activation. Inhibitors of PI3K coordinately decreased phospho-PKCiota and Cyclin E protein levels. In conclusion, we have identified a PI3K/PKCiota/Cyclin E signaling pathway as a therapeutic target during ovarian tumorigenesis. PMID:26279297

  3. hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions

    PubMed Central

    2012-01-01

    Background Gastric cancer is a serious public health problem in Northern Brazil and in the world due to its high incidence and mortality. Despite the severity of the disease, more research is needed to better understand the molecular events involved in this intestinal-type gastric carcinogenesis process. Since precancerous lesions precede intestinal-type gastric cancer, here, we evaluated the hTERT, MYC, and TP53 mRNA and protein expression, as well as TP33 copy number, in gastric preneoplastic lesions. Methods We evaluated 19 superficial gastritis, 18 atrophic gastritis, and 18 intestinal metaplasia from cancer-free individuals of Northern Brazil. Quantitative reverse transcription PCR was used to analyze the mRNA expression and immunohistochemical methods were used to assess protein immunoreactivity in tissue samples. The number of TP53 gene copies was investigated in gastric diseases by quantitative PCR. Results We observed hTERT, MYC, and p53 immunoreactivity only in intestinal metaplasia samples. The immunoreactivity of these proteins was strongly associated with each other. A significantly higher MYC mRNA expression was observed in intestinal metaplasia compared to gastritis samples. Loss of TP53 was also only detected in intestinal metaplasia specimens. Conclusions We demonstrated that hTERT, MYC, and TP53 are deregulated in intestinal metaplasia of individuals from Northern Brazil and these alterations may facilitate tumor initiation. PMID:22768805

  4. [Effects of pharmacy market deregulation regarding patient-centred drug care in Germany from a health economics perspecitve].

    PubMed

    Rumm, R; Böcking, W

    2013-03-01

    This article analyses the impact of a potential deregulation Germany's pharmacy market by allowing foreign ownership of pharmacies and removing the limit of the number pharmacies that can be owned by a pharmacist. Based on a mathematical model and empirical values of foreign countries, scenarios for the German market are calculated and the impact on all participants of the health care system analysed. The key outcomes are:- A deregulation would enables the creation of pharmacy chains- In all simulated scenarios the total number of pharmacies would drastically grow- The increased pharmacy density improves patient centred drug care- The competition among pharmacies increases and leads to the closure of many independently owned and operated pharmacies.

  5. 77 FR 4547 - Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-30

    ... Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant Programs... requests and documents from postsecondary institutions for the Federal Perkins Loan, Federal Work-Study.... (2) General Provisions for the Federal Perkins Loan Program, Federal Work-Study Program, and...

  6. 78 FR 14776 - Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-07

    ... Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant Programs... requests and documents from postsecondary institutions for the Federal Perkins Loan, Federal Work-Study..., Federal Work-Study Program, and Federal Supplemental Educational Opportunity Grant Program, 34 CFR...

  7. 75 FR 12217 - Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-15

    ... Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant programs... Perkins Loan, Federal Work-Study (FWS), and Federal Supplemental Educational Opportunity Grant (FSEOG.... (2) General Provisions for the Federal Perkins Loan Program, Federal Work-Study Program, and...

  8. Gene expression profiling to identify markers associated with deregulated hTERT in HPV-transformed keratinocytes and cervical cancer.

    PubMed

    de Wilde, Jillian; Wilting, Saskia M; Meijer, Chris J L M; van de Wiel, Mark A; Ylstra, Bauke; Snijders, Peter J F; Steenbergen, Renske D M

    2008-02-15

    Although high-risk human papillomavirus (HPV) infection plays a major role in the development of cervical cancer, additive oncogenic events are involved as well. One key event involves increased activity of telomerase resulting from a deregulated expression of its catalytic subunit hTERT. Our previous microcell-mediated chromosome transfer studies revealed that introduction of human chromosome 6 in the HPV16-immortalized keratinocyte cell line FK16A and in the HPV16-containing cervical cancer cell line SiHa induced growth arrest, resulting from a repression of hTERT mRNA expression and telomerase activity. Here, this model was used to analyze expression profiles associated with hTERT deregulation in HPV-transformed cells. Microarray expression analysis of 12 FK16A/chromosome 6 hybrids, 4 of which were negative for endogenous hTERT and 8 of which were positive for endogenous hTERT, resulted in the identification of 164 differentially expressed genes. Differential expression of a selection of 5 genes was verified by real-time RT-PCR. Of these 164 genes, 32 were also differentially expressed in other HPV transformed cells with deregulated hTERT. For 2 of these genes, encoding AQP3 and MGP, altered expression in hTERT positive cervical carcinomas was confirmed by real-time RT-PCR and immunohistochemistry, respectively. Moreover, increased MGP protein expression was significantly more frequent in high-grade cervical premalignant lesions with elevated hTERT mRNA expression compared to those without. In summary, we identified 32 candidate biomarkers for deregulated hTERT mRNA expression, which may enable the identification of cervical premalignant lesions that are at highest risk to progress to invasive cancer.

  9. Deregulation of subcellular biometal homeostasis through loss of the metal transporter, Zip7, in a childhood neurodegenerative disorder

    PubMed Central

    2014-01-01

    Background Aberrant biometal metabolism is a key feature of neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. Metal modulating compounds are promising therapeutics for neurodegeneration, but their mechanism of action remains poorly understood. Neuronal ceroid lipofuscinoses (NCLs), caused by mutations in CLN genes, are fatal childhood neurodegenerative lysosomal storage diseases without a cure. We previously showed biometal accumulation in ovine and murine models of the CLN6 variant NCL, but the mechanism is unknown. This study extended the concept that alteration of biometal functions is involved in pathology in these disorders, and investigated molecular mechanisms underlying impaired biometal trafficking in CLN6 disease. Results We observed significant region-specific biometal accumulation and deregulation of metal trafficking pathways prior to disease onset in CLN6 affected sheep. Substantial progressive loss of the ER/Golgi-resident Zn transporter, Zip7, which colocalized with the disease-associated protein, CLN6, may contribute to the subcellular deregulation of biometal homeostasis in NCLs. Importantly, the metal-complex, ZnII(atsm), induced Zip7 upregulation, promoted Zn redistribution and restored Zn-dependent functions in primary mouse Cln6 deficient neurons and astrocytes. Conclusions This study demonstrates the central role of the metal transporter, Zip7, in the aberrant biometal metabolism of CLN6 variants of NCL and further highlights the key contribution of deregulated biometal trafficking to the pathology of neurodegenerative diseases. Importantly, our results suggest that ZnII(atsm) may be a candidate for therapeutic trials for NCLs. PMID:24581221

  10. PML-RARA-associated cooperating mutations belong to a transcriptional network that is deregulated in myeloid leukemias.

    PubMed

    Ronchini, C; Brozzi, A; Riva, L; Luzi, L; Gruszka, A M; Melloni, G E M; Scanziani, E; Dharmalingam, G; Mutarelli, M; Belcastro, V; Lavorgna, S; Rossi, V; Spinelli, O; Biondi, A; Rambaldi, A; Lo-Coco, F; di Bernardo, D; Pelicci, P G

    2017-01-20

    It has been shown that individual acute myeloid leukemia (AML) patients are characterized by one of few initiating DNA mutations and 5-10 cooperating mutations not yet defined among hundreds identified by massive sequencing of AML genomes. We report an in vivo insertional-mutagenesis screen for genes cooperating with one AML initiating mutations (PML-RARA, oncogene of acute promyelocytic leukemia, APL), which allowed identification of hundreds of genetic cooperators. The cooperators are mutated at low frequency in APL or AML patients but are always abnormally expressed in a cohort of 182 APLs and AMLs analyzed. These deregulations appear non-randomly distributed and present in all samples, regardless of their associated genomic mutations. Reverse-engineering approaches showed that these cooperators belong to a single transcriptional gene network, enriched in genes mutated in AMLs, where perturbation of single genes modifies expression of others. Their gene-ontology analysis showed enrichment of genes directly involved in cell proliferation control. Therefore, the pool of PML-RARA cooperating mutations appears large and heterogeneous, but functionally equivalent and deregulated in the majority of APLs and AMLs. Our data suggest that the high heterogeneity of DNA mutations in APLs and AMLs can be reduced to patterns of gene expression deregulation of a single 'mutated' gene network.Leukemia advance online publication, 20 January 2017; doi:10.1038/leu.2016.386.

  11. Federal Employees' Compensation Act.

    PubMed

    Ladou, Joseph

    2009-01-01

    The Federal Employees' Compensation Act (FECA) program provides wage loss compensation and payments for medical treatment to federal civilian employees. Administered by the Department of Labor (DOL), FECA covers over 2.7 million federal employees in more than 70 different agencies. FECA costs rose from $1.4 billion in 1990 to $2.6 in 2006, while the federal workforce remained essentially unchanged. While federal civilian employees represent only 2.1% of all workers eligible for workers' compensation benefits, federal programs account for 6% of the benefits paid. Disability benefits under FECA are far greater than those in the state workers' compensation programs. The benefit payments often exceed the former salary of the injured employee. The last congressional hearings on the FECA program were held over thirty years ago. It is unlikely that Congressional review will occur any time soon, as the entrenched bureaucracy that benefits from the FECA program defines and protects its future.

  12. Application Kit for Federal Assistance

    EPA Pesticide Factsheets

    The Federal Grant & Cooperative Agreement Act of 1977 requires Federal agencies to use a contract to acquire property or services that directly benefit the Federal government.This letter to the applicant explains the Application Kit for Federal Assistance.

  13. Federal Agency and Federal Library Reports.

    ERIC Educational Resources Information Center

    Williams, Jane; Wooding, Janet E.; Lisowski, Lori A.; Borys, Cynthia; Chute, Adrienne; Fischer, Audrey; Cole, John Y.; Tarr, Susan M.; Norris, Brian; Mehnert, Robert; Brandhorst, Ted; Sherman, Andrew M.

    1998-01-01

    Contains reports from National Commission on Libraries and Information Science, National Technical Information Service, National Archives, U.S. Information Agency, National Center for Education Statistics, Library of Congress, Center for the Book, Federal Library and Information Center Committee, National Agricultural Library, National Library of…

  14. Federal Agency and Federal Library Reports.

    ERIC Educational Resources Information Center

    Wooding, Janet E; Lisowski, Lori A.; Gilliam, Bo; Chute, Adrienne; Fischer, Audrey; Cole, John Y.; Tarr, Susan M.; Norris, Brian; Mehnert, Robert; Brandhorst, Ted; Sherman, Andrew M.; Willard, Robert S.

    1999-01-01

    Presents reports from: National Technical Information Service; National Archives and Records Administration; United States Information Agency; National Center for Educational Statistics Library Statistics Cooperative Program; Library of Congress; Center for the Book; Federal Library and Information Center Committee; National Agricultural Library;…

  15. Expression of the Retrotransposon Helena Reveals a Complex Pattern of TE Deregulation in Drosophila Hybrids

    PubMed Central

    Romero-Soriano, Valèria; Garcia Guerreiro, Maria Pilar

    2016-01-01

    Transposable elements (TEs), repeated mobile sequences, are ubiquitous in the eukaryotic kingdom. Their mobilizing capacity confers on them a high mutagenic potential, which must be strongly regulated to guarantee genome stability. In the Drosophila germline, a small RNA-mediated silencing system, the piRNA (Piwi-interacting RNA) pathway, is the main responsible TE regulating mechanism, but some stressful conditions can destabilize it. For instance, during interspecific hybridization, genomic stress caused by the shock of two different genomes can lead, in both animals and plants, to higher transposition rates. A recent study in D. buzatii—D. koepferae hybrids detected mobilization of 28 TEs, yet little is known about the molecular mechanisms explaining this transposition release. We have characterized one of the mobilized TEs, the retrotransposon Helena, and used quantitative expression to assess whether its high transposition rates in hybrids are preceded by increased expression. We have also localized Helena expression in the gonads to see if cellular expression patterns have changed in the hybrids. To give more insight into changes in TE regulation in hybrids, we analysed Helena-specific piRNA populations of hybrids and parental species. Helena expression is not globally altered in somatic tissues, but male and female gonads have different patterns of deregulation. In testes, Helena is repressed in F1, increasing then its expression up to parental values. This is linked with a mislocation of Helena transcripts along with an increase of their specific piRNA levels. Ovaries have additive levels of Helena expression, but the ping-pong cycle efficiency seems to be reduced in F1 hybrids. This could be at the origin of new Helena insertions in hybrids, which would be transmitted to F1 hybrid female progeny. PMID:26812285

  16. Identification of Novel Deregulated RNA Metabolism-Related Genes in Non-Small Cell Lung Cancer

    PubMed Central

    Valles, Iñaki; Pajares, Maria J.; Segura, Victor; Guruceaga, Elisabet; Gomez-Roman, Javier; Blanco, David; Tamura, Akiko; Montuenga, Luis M.; Pio, Ruben

    2012-01-01

    Lung cancer is a leading cause of cancer death worldwide. Several alterations in RNA metabolism have been found in lung cancer cells; this suggests that RNA metabolism-related molecules are involved in the development of this pathology. In this study, we searched for RNA metabolism-related genes that exhibit different expression levels between normal and tumor lung tissues. We identified eight genes differentially expressed in lung adenocarcinoma microarray datasets. Of these, seven were up-regulated whereas one was down-regulated. Interestingly, most of these genes had not previously been associated with lung cancer. These genes play diverse roles in mRNA metabolism: three are associated with the spliceosome (ASCL3L1, SNRPB and SNRPE), whereas others participate in RNA-related processes such as translation (MARS and MRPL3), mRNA stability (PCBPC1), mRNA transport (RAE), or mRNA editing (ADAR2, also known as ADARB1). Moreover, we found a high incidence of loss of heterozygosity at chromosome 21q22.3, where the ADAR2 locus is located, in NSCLC cell lines and primary tissues, suggesting that the downregulation of ADAR2 in lung cancer is associated with specific genetic losses. Finally, in a series of adenocarcinoma patients, the expression of five of the deregulated genes (ADAR2, MARS, RAE, SNRPB and SNRPE) correlated with prognosis. Taken together, these results support the hypothesis that changes in RNA metabolism are involved in the pathogenesis of lung cancer, and identify new potential targets for the treatment of this disease. PMID:22876301

  17. Deregulation of inflammatory response in the diabetic condition is associated with increased ischemic brain injury

    PubMed Central

    2014-01-01

    Background Although elicited inflammation contributes to tissue injury, a certain level of inflammation is necessary for subsequent tissue repair/remodeling. Diabetes, a chronic low-grade inflammatory state, is a predisposing risk factor for stroke. The condition is associated with delayed wound healing, presumably due to disrupted inflammatory responses. With inclusion of the diabetic condition in an experimental animal model of stroke, this study investigates whether the condition alters inflammatory response and influences stroke-induced brain injury. Methods C57BL/6 mice were fed a diabetic diet (DD) for 8 weeks to induce an experimental diabetic condition or a normal diet (ND) for the same duration. Gene expression of inflammatory factors including monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), CCR2, and CD36 was assessed in the peripheral immune cells and brains of normal and diabetic mice before and after focal cerebral ischemia. The expression of these factors was also determined in lipopolysaccharide (LPS)-treated cultured normal and diabetic macrophages. Ischemic outcome was assessed in these mice at 3 days post-ischemia. Results DD intervention in mice resulted in obesity and elevated insulin and glucose level in the blood. The peritoneal immune cells from the diabetic mice showed higher MCP-1 mRNA levels before and after stroke. Compared to normal mice, diabetic mice showed reduced MCP-1, IL-6, and CCR2 gene expression in the brain at 6 h post-ischemia. LPS-stimulated inflammatory responses were also reduced in the diabetic macrophages. The diabetic mice showed larger infarct size and percent swelling. Conclusions These results showed that diabetic conditions deregulate acute inflammatory response and that the condition is associated with increased stroke-induced injury. The study suggests that interventions aimed at restoring appropriate inflammatory response in peripheral immune cells/macrophages may be beneficial in reducing

  18. MiR-194 Deregulation Contributes To Colorectal Carcinogenesis via Targeting AKT2 Pathway

    PubMed Central

    Zhao, Hui-Jun; Ren, Lin-Lin; Wang, Zhen-Hua; Sun, Tian-Tian; Yu, Ya-Nan; Wang, Ying-Chao; Yan, Ting-Ting; Zou, Weiping; He, Jie; Zhang, Yaou; Hong, Jie; Fang, Jing-Yuan

    2014-01-01

    Abstract: Recent studies have increasingly linked microRNAs to colorectal cancer (CRC). MiR-194 has been reported deregulated in different tumor types, whereas the function of miR-194 in CRC largely remains unexplored. Here we investigated the biological effects, mechanisms and clinical significance of miR-194. Functional assay revealed that overexpression of miR-194 inhibited CRC cell viability and invasion in vitro and suppressed CRC xenograft tumor growth in vivo. Conversely, block of miR-194 in APCMin/+ mice promoted tumor growth. Furthermore, miR-194 reduced the expression of AKT2 both in vitro and in vivo. Clinically, the expression of miR-194 gradually decreased from 20 normal colorectal mucosa (N-N) cases through 40 colorectal adenomas (CRA) cases and then to 40 CRC cases, and was negatively correlated with AKT2 and pAKT2 expression. Furthermore, expression of miR-194 in stool samples was gradually decreased from 20 healthy cases, 20 CRA cases, then to 28 CRC cases. Low expression of miR-194 in CRC tissues was associated with large tumor size (P=0.006), lymph node metastasis (P=0.012) and shorter survival (HR =2.349, 95% CI = 1.242 to 4.442; P=0.009). In conclusion, our data indicated that miR-194 acted as a tumor suppressor in the colorectal carcinogenesis via targeting PDK1/AKT2/XIAP pathway, and could be a significant diagnostic and prognostic biomarker for CRC. PMID:25285168

  19. Deregulation of Ion Channel and Transporter Encoding Genes in Pediatric Gliomas

    PubMed Central

    Masselli, Marika; Laise, Pasquale; Tonini, Giulia; Fanelli, Duccio; Pillozzi, Serena; Cetica, Valentina; Da Ros, Martina; Sardi, Iacopo; Buccoliero, Anna Maria; Aricò, Maurizio; Genitori, Lorenzo; Becchetti, Andrea; Arcangeli, Annarosa

    2012-01-01

    Brain tumors, including the majority gliomas, are the leading cause of cancer-related death in children. World Health Organization has divided pediatric brain tumors into different grades and, based upon cDNA microarray data identifying gene expression profiles (GEPs), it has become evident in the last decade that the various grades involve different types of genetic alterations. However, it is not known whether ion channel and transporter genes, intimately involved in brain functioning, are associated with such GEPs. We determined the GEPs in an available cohort of 10 pediatric brain tumors initially by comparing the data obtained from four primary tumor samples and corresponding short-term cultures. The correspondence between the two types of samples was statistically significant. We then performed bioinformatic analyses on those samples (a total of nine) which corresponded to tumors of glial origin, either tissues or cell cultures, depending on the best “RNA integrity number.” We used R software to evaluate the genes which were differentially expressed (DE) in gliomas compared with normal brain. Applying a p-value below 0.01 and fold change ≥4, led to identification of 2284 DE genes. Through a Functional Annotation Analysis (FAA) using the NIH-DAVID software, the DE genes turned out to be associated mainly with: immune/inflammatory response, cell proliferation and survival, cell adhesion and motility, neuronal phenotype, and ion transport. We have shown that GEPs of pediatric brain tumors can be studied using either primary tumor samples or short-term cultures with similar results. From FAA, we concluded that, among DE genes, pediatric gliomas show a strong deregulation of genes related to ion channels and transporters. PMID:22662319

  20. Deregulated Sex Chromosome Gene Expression with Male Germ Cell-Specific Loss of Dicer1

    PubMed Central

    Snyder, Elizabeth; Buaas, F. William; Gu, Tongjun; Stearns, Timothy M.; Sharma, Manju; Murchison, Elizabeth P.; Puente, Gabriella C.; Braun, Robert E.

    2012-01-01

    MicroRNAs (miRNAs) are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNase III endonuclease encoded by Dicer1, is required for processing short 21–22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility. Reduced levels of Dicer1 transcripts and DICER1 were confirmed in germ cell knock-out (GCKO) testes by postnatal day 18 (P18). Compared to wild-type (WT) at 8 weeks, GCKO males had no change in body weight; yet showed significant reductions in testis mass and sperm number. Histology and fertility tests confirmed spermatogenic failure in GCKO males. Array analyses at P18 showed that in comparison to WT testes, 75% of miRNA genes and 37% of protein coding genes were differentially expressed in GCKO testes. Among these, 96% of miRNA genes were significantly down-regulated, while 4% miRNA genes were overexpressed. Interestingly, we observed preferential overexpression of genes encoded on the sex chromosomes in GCKO testes, including more than 80% of previously identified targets of meiotic sex chromosome inactivation (MSCI). Compared to WT, GCKO mice showed higher percentages of germ cells at early meiotic stages (leptotene and zygotene) but lower percentages at later stages (pachytene, diplotene and metaphase I) providing evidence that deletion of Dicer1 leads to disruptions in meiotic progression. Therefore, deleting Dicer1 in early postnatal germ cells resulted in deregulation of transcripts encoded by genes on the sex chromosomes, impaired meiotic progression and led to spermatogenic failure and infertility. PMID:23056286

  1. Deregulated expression of VHL mRNA variants in papillary thyroid cancer.

    PubMed

    Baldini, Enke; Tuccilli, Chiara; Arlot-Bonnemains, Yannick; Chesnel, Frank; Sorrenti, Salvatore; De Vito, Corrado; Catania, Antonio; D'Armiento, Eleonora; Antonelli, Alessandro; Fallahi, Poupak; Watutantrige-Fernando, Sara; Tartaglia, Francesco; Barollo, Susi; Mian, Caterina; Bononi, Marco; Arceri, Stefano; Mascagni, Domenico; Vergine, Massimo; Pironi, Daniele; Monti, Massimo; Filippini, Angelo; Ulisse, Salvatore

    2017-03-05

    Recent findings demonstrated that a subset of papillary thyroid cancers (PTCs) is characterized by reduced expression of the von Hippel-Lindau (VHL) tumor suppressor gene, and that lowest levels associated with more aggressive PTCs. In the present study, the levels of the two VHL mRNA splicing variants, VHL-213 (V1) and VHL-172 (V2), were measured in a series of 96 PTC and corresponding normal matched tissues by means of quantitative RT-PCR. Variations in the mRNA levels were correlated with patients' clinicopathological parameters and disease-free interval (DFI). The analysis of VHL mRNA in tumor tissues, compared to normal matched tissues, revealed that its expression was either up- or down-regulated in the majority of PTC. In particular, V1 and V2 mRNA levels were altered, respectively, in 78 (81.3%) and 65 (67.7%) out of the 96 PTCs analyzed. A significant positive correlation between the two mRNA variants was observed (p < 0.001). Univariate analysis documented the lack of association between each variant and clinicopathological parameters such as age, tumor size, histology, TNM stage, lymph node metastases, and BRAF mutational status. However, a strong correlation was found between altered V1 or V2 mRNA levels and DFI. Multivariate regression analysis indicated higher V1 mRNA values, along with lymph node metastases at diagnosis, as independent prognostic factors predicting DFI. In conclusion, the data reported demonstrate that VHL gene expression is deregulated in the majority of PTC tissues. Of particular interest is the apparent protective role exerted by VHL transcripts against PTC recurrences.

  2. Deregulated sex chromosome gene expression with male germ cell-specific loss of Dicer1.

    PubMed

    Greenlee, Anne R; Shiao, Meng-Shin; Snyder, Elizabeth; Buaas, F William; Gu, Tongjun; Stearns, Timothy M; Sharma, Manju; Murchison, Elizabeth P; Puente, Gabriella C; Braun, Robert E

    2012-01-01

    MicroRNAs (miRNAs) are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNase III endonuclease encoded by Dicer1, is required for processing short 21-22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility. Reduced levels of Dicer1 transcripts and DICER1 were confirmed in germ cell knock-out (GCKO) testes by postnatal day 18 (P18). Compared to wild-type (WT) at 8 weeks, GCKO males had no change in body weight; yet showed significant reductions in testis mass and sperm number. Histology and fertility tests confirmed spermatogenic failure in GCKO males. Array analyses at P18 showed that in comparison to WT testes, 75% of miRNA genes and 37% of protein coding genes were differentially expressed in GCKO testes. Among these, 96% of miRNA genes were significantly down-regulated, while 4% miRNA genes were overexpressed. Interestingly, we observed preferential overexpression of genes encoded on the sex chromosomes in GCKO testes, including more than 80% of previously identified targets of meiotic sex chromosome inactivation (MSCI). Compared to WT, GCKO mice showed higher percentages of germ cells at early meiotic stages (leptotene and zygotene) but lower percentages at later stages (pachytene, diplotene and metaphase I) providing evidence that deletion of Dicer1 leads to disruptions in meiotic progression. Therefore, deleting Dicer1 in early postnatal germ cells resulted in deregulation of transcripts encoded by genes on the sex chromosomes, impaired meiotic progression and led to spermatogenic failure and infertility.

  3. Epigenetic deregulation of Ellis Van Creveld confers robust Hedgehog signaling in adult T-cell leukemia.

    PubMed

    Takahashi, Ryutaro; Yamagishi, Makoto; Nakano, Kazumi; Yamochi, Toshiko; Yamochi, Tadanori; Fujikawa, Dai; Nakashima, Makoto; Tanaka, Yuetsu; Uchimaru, Kaoru; Utsunomiya, Atae; Watanabe, Toshiki

    2014-09-01

    One of the hallmarks of cancer, global gene expression alteration, is closely associated with the development and malignant characteristics associated with adult T-cell leukemia (ATL) as well as other cancers. Here, we show that aberrant overexpression of the Ellis Van Creveld (EVC) family is responsible for cellular Hedgehog (HH) activation, which provides the pro-survival ability of ATL cells. Using microarray, quantitative RT-PCR and immunohistochemistry we have demonstrated that EVC is significantly upregulated in ATL and human T-cell leukemia virus type I (HTLV-1)-infected cells. Epigenetic marks, including histone H3 acetylation and Lys4 trimethylation, are specifically accumulated at the EVC locus in ATL samples. The HTLV-1 Tax participates in the coordination of EVC expression in an epigenetic fashion. The treatment of shRNA targeting EVC, as well as the transcription factors for HH signaling, diminishes the HH activation and leads to apoptotic death in ATL cell lines. We also showed that a HH signaling inhibitor, GANT61, induces strong apoptosis in the established ATL cell lines and patient-derived primary ATL cells. Therefore, our data indicate that HH activation is involved in the regulation of leukemic cell survival. The epigenetically deregulated EVC appears to play an important role for HH activation. The possible use of EVC as a specific cell marker and a novel drug target for HTLV-1-infected T-cells is implicated by these findings. The HH inhibitors are suggested as drug candidates for ATL therapy. Our findings also suggest chromatin rearrangement associated with active histone markers in ATL.

  4. Deregulation of the planar cell polarity genes CELSR3 and FZD3 in Hirschsprung disease.

    PubMed

    Su, Lin; Zhang, Zhen; Gan, Liang; Jiang, Qian; Xiao, Ping; Zou, Jizhen; Li, Qi; Jiang, Hong

    2016-10-01

    Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence of intrinsic ganglion cells in the lower intestine. Genetic factors in the pathogenesis of this disease are under active investigation. As core genes in the planar cell polarity pathway, Celsr3 and Fzd3 are believed to play vital roles in the development of the murine enteric nervous system. The potential association of CELSR3 and FZD3 with the development of HSCR in humans, however, is still unknown. We determined the genotypes of eight CELSR3 and FZD3 polymorphisms in 113 patients. Furthermore, target gene sequencing was used to search for rare mutations in the planar cell polarity genes. The mRNA and protein expression of CELSR3 and FZD3 were explored in patients with HSCR. Class III β-tubulin in colon tissue samples was examined to elucidate enteric innervation patterns. We observed a significant association between the FZD3 rs17059206 polymorphism and HSCR susceptibility (p<0.001). In addition, five rare mutations in CELSR3 were identified in six patients with HSCR. Upregulation of CELSR3 mRNA expression was detected in 80% of aganglionic segments; a similar increase was found for FZD3 protein expression in 81.8% of aganglionic tissues, compared with the ganglionic segments. Immunohistochemical staining on tissue sections revealed obvious excess expression of both molecules in the mucosal layer. The neurite patterns were highly disorganized in the aganglionic bowel segments, with a marked reduction in the prominence of TUJ1 bundles in number, thickness, and length. Our results showed that deregulation of the planar cell polarity genes CELSR3 and FZD3 might disrupt the enteric innervation pattern and consequently contribute to the susceptibility to HSCR.

  5. Deregulation of polycomb repressor complex 1 modifier AUTS2 in T-cell leukemia

    PubMed Central

    Nagel, Stefan; Pommerenke, Claudia; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G.; MacLeod, Roderick A.F.

    2016-01-01

    Recently, we identified deregulated expression of the B-cell specific transcription factor MEF2C in T-cell acute lymphoid leukemia (T-ALL). Here, we performed sequence analysis of a regulatory upstream section of MEF2C in T-ALL cell lines which, however, proved devoid of mutations. Unexpectedly, we found strong conservation between the regulatory upstream region of MEF2C (located at chromosomal band 5q14) and an intergenic stretch at 7q11 located between STAG3L4 and AUTS2, covering nearly 20 kb. While the non-coding gene STAG3L4 was inconspicuously expressed, AUTS2 was aberrantly upregulated in 6% of T-ALL patients (public dataset GSE42038) and in 3/24 T-ALL cell lines, two of which represented very immature differentiation stages. AUTS2 expression was higher in normal B-cells than in T-cells, indicating lineage-specific activity in lymphopoiesis. While excluding chromosomal aberrations, examinations of AUTS2 transcriptional regulation in T-ALL cells revealed activation by IL7-IL7R-STAT5-signalling and MEF2C. AUTS2 protein has been shown to interact with polycomb repressor complex 1 subtype 5 (PRC1.5), transforming this particular complex into an activator. Accordingly, expression profiling and functional analyses demonstrated that AUTS2 activated while PCGF5 repressed transcription of NKL homeobox gene MSX1 in T-ALL cells. Forced expression and pharmacological inhibition of EZH2 in addition to H3K27me3 analysis indicated that PRC2 repressed MSX1 as well. Taken together, we found that AUTS2 and MEF2C, despite lying on different chromosomes, share strikingly similar regulatory upstream regions and aberrant expression in T-ALL subsets. Our data implicate chromatin complexes PRC1/AUTS2 and PRC2 in a gene network in T-ALL regulating early lymphoid differentiation. PMID:27322685

  6. Deregulation of arginase induces bone complications in high-fat/high-sucrose diet diabetic mouse model.

    PubMed

    Bhatta, Anil; Sangani, Rajnikumar; Kolhe, Ravindra; Toque, Haroldo A; Cain, Michael; Wong, Abby; Howie, Nicole; Shinde, Rahul; Elsalanty, Mohammed; Yao, Lin; Chutkan, Norman; Hunter, Monty; Caldwell, Ruth B; Isales, Carlos; Caldwell, R William; Fulzele, Sadanand

    2016-02-15

    A balanced diet is crucial for healthy development and prevention of musculoskeletal related diseases. Diets high in fat content are known to cause obesity, diabetes and a number of other disease states. Our group and others have previously reported that activity of the urea cycle enzyme arginase is involved in diabetes-induced dysregulation of vascular function due to decreases in nitric oxide formation. We hypothesized that diabetes may also elevate arginase activity in bone and bone marrow, which could lead to bone-related complications. To test this we determined the effects of diabetes on expression and activity of arginase, in bone and bone marrow stromal cells (BMSCs). We demonstrated that arginase 1 is abundantly present in the bone and BMSCs. We also demonstrated that arginase activity and expression in bone and bone marrow is up-regulated in models of diabetes induced by HFHS diet and streptozotocin (STZ). HFHS diet down-regulated expression of healthy bone metabolism markers (BMP2, COL-1, ALP, and RUNX2) and reduced bone mineral density, bone volume and trabecular thickness. However, treatment with an arginase inhibitor (ABH) prevented these bone-related complications of diabetes. In-vitro study of BMSCs showed that high glucose treatment increased arginase activity and decreased nitric oxide production. These effects were reversed by treatment with an arginase inhibitor (ABH). Our study provides evidence that deregulation of l-arginine metabolism plays a vital role in HFHS diet-induced diabetic complications and that these complications can be prevented by treatment with arginase inhibitors. The modulation of l-arginine metabolism in disease could offer a novel therapeutic approach for osteoporosis and other musculoskeletal related diseases.

  7. Federal Legislative Proposals, 1969.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO.

    The commission outlined a legislative program at the Federal level. Federal aid should come under the direct control of the executive branch to consolidate and simplify all education aid programs. This reorganization should include continuous and effective presentation of the State point of view to the responsible authorities. A new three-tiered…

  8. Navigating the new deregulated landscape: Opportunities and risks for wind energy

    SciTech Connect

    Fossum, D.J.; Hill, D.R.

    1997-12-31

    Major changes in the law governing the electric industry are underway, fundamentally altering how the generation and sale of electric power is regulated and how electric power is marketed in the United States. Legislative and regulatory initiatives promoting competition will create a variety of opportunities, and commensurate risks, for power generators, marketers, brokers, sellers, and purchasers. To succeed in the new marketplace, suppliers of renewable energy must understand the changes occurring on the state and federal levels, and position themselves to take advantage of the opportunities available. In this environment, monitoring and participating in state and federal legislative and regulatory efforts will be crucial for maximizing opportunities for wind energy.

  9. An Interdisciplinary Look at Minorities and the Media: Implications for Deregulation.

    ERIC Educational Resources Information Center

    Wimmer, Kurt A.; Wright, Jay B.

    Two contradictory trends are developing in telecommunications. The first is increased viewing of television by minorities, while the second is decreased attention given to minority issues by the Federal Communications Commission's (FCC) deregulatory stance. Minority groups consume more television than any other social groups, yet television's…

  10. Deregulation of the Electric Industry and Its Potential Benefits for School Districts.

    ERIC Educational Resources Information Center

    Watkiss, Jeffrey D.

    1997-01-01

    The electric utility industry is the last bastion of regulated monopolies in the United States. An overview of recent competition in the electric-power industry at both the federal and state levels and how this may affect school districts is offered in this article. The text identifies and evaluates how school districts can obtain cheaper power…

  11. Federalism, Agenda Setting, and the Dynamics of Federal Education Policy.

    ERIC Educational Resources Information Center

    Manna, Paul

    This paper is part of a larger project on agenda setting in the U.S. federal system and the development of the federal education agenda since 1965. Two questions motivate the paper, one theoretical and the other empirical: (1) how does federalism affect the federal agenda?; and (2) what explains the development of federal involvement in K-12…

  12. Early2 factor (E2F) deregulation is a prognostic and predictive biomarker in lung adenocarcinoma

    PubMed Central

    Chen, Lu; Kurtyka, Courtney A; Welsh, Eric A; Engel, Brienne E; Muñoz-Antonia, Teresita; Yoder, Sean J; Eschrich, Steven A; Creelan, Ben C; Chiappori, Alberto A; Gray, Jhanelle E; Ramirez, Jose Luis; Rosell, Rafael; Schabath, Matthew B; Haura, Eric B; Chen, Dung-Tsa; Cress, Douglas W

    2016-01-01

    Clinicians routinely prescribe adjuvant chemotherapy (ACT) for resected non-small cell lung cancer patients. However, ACT only improves five-year disease-free survival in stage I-III non-small cell lung cancer by 5-15%, with most patients deriving no benefit. Herein, deregulation of the E2F pathway was explored as a biomarker in lung adenocarcinoma patients. An E2F pathway scoring system, based on 74 E2F-regulated genes, was trained for RNA from two platforms: fresh-frozen (FF) or formalin-fixed paraffin-embedded (FFPE) tissues. The E2F score was tested as a prognostic biomarker in five FF-based cohorts and two FFPE-based cohorts. The E2F score was tested as a predictive biomarker in two randomized clinical trials; JBR10 and the NATCH (Neo-Adjuvant Taxol-Carboplatin Hope) trial. The E2F score was prognostic in untreated patients in all seven datasets examined (p < 0.05). Stage-specific analysis of combined cohorts demonstrated that the E2F score was prognostic in stage I patients (p = 0.0495 to <0.001; hazard ratio, HR, =2.04- 2.22) with a similar trend in other stages. The E2F score was strongly predictive in stage II patients from the two combined randomized clinical trials with a significant differential treatment effect (p = 0.015). Specifically, ACT improved survival in stage II patients with high E2F (p = 0.01; HR= 0.21). The 5-year survival increased from 18% to 81%. In contrast, in patients with low E2F, 5-year survival was 57% in untreated patients and 41% in ACT-treated patients with a HR of 1.55 (p = 0.47). In summary, the E2F score provides valuable prognostic information for Stage I and predictive information for Stage II lung adenocarcinoma patients and should be further explored as a decision support tool for their treatment. PMID:27756884

  13. Federal Sector Negotiability

    DTIC Science & Technology

    1989-01-01

    LogisticsCouncil v. Federal Labor Relations Authority, 810 F.2d 234, 241- 242 (D.C. Cir. 1987); Circuit Judge D.H. Ginsburg writing for the court in United...concurring and dissenting in Defense Logistics Council v. Federal Labor Relations Authority, 810 F.2d 234, 241- 242 (D.C. Cir. 1987); Judge D.H. Ginsburg...cert. dismissed 106 S.Ct. 1678 (1986) (per curium ); American Federation of State. County and Municipal Employees. Local 3097 and Department of Justice

  14. Expression of lumbosacral HOX genes, crucial in kidney organogenesis, is systematically deregulated in clear cell kidney cancers.

    PubMed

    Cantile, Monica; Schiavo, Giulia; Franco, Renato; Cindolo, Luca; Procino, Alfredo; D'Armiento, Maria; Facchini, Gaetano; Terracciano, Luigi; Botti, Gerardo; Cillo, Clemente

    2011-06-01

    Homeobox-containing genes are involved in different stages of kidney organogenesis, from the early events in intermediate mesoderm to terminal differentiation of glomerular and tubular epithelia. The HOX genes show a unique genomic network organization and regulate normal development. The targeted disruption of paralogous group 11 HOX genes (HOX A11, HOX C11 and HOX D11) results in a complete loss of metanephric kidney induction. Despite a large amount of data are related to the early events in the kidney development, not much is known about HOX genes in advanced kidney organogenesis and carcinogenesis. Here, we compare the expression of the whole HOX gene network in late-stage human foetal kidney development with the same patterns detected in 25 pairs of normal clear cell renal carcinomas (RCCs) and 15 isolated RCC biopsy samples. In the majority of RCCs tested, HOX C11 is upregulated, whereas HOX D11, after an early involvement becomes active again at the 23rd week of the foetal kidney development, is always expressed in normal adult kidneys and is deregulated, together with HOX A11 and lumbosacral locus D HOX genes. Thus, through its function of regulating phenotype cell identity, the HOX network plays an important role in kidney carcinogenesis. Lumbosacral HOX genes are involved in the molecular alterations associated with clear cell kidney cancers and represent, through their deregulation, a molecular mark of tubular epithelial dedifferentiation occurring along tumour evolution, with the restoration of genetic programs associated with kidney organogenesis. The deregulation of lumbosacral HOX genes in RCCs supports (i) the consideration of the HOX gene transcriptome as the potential prognostic tool in kidney carcinogenesis and (ii) the possibility to foresee clinical trials with the purpose of targeting these genes to achieve a therapeutic effect in RCC patients.

  15. Deregulated microRNAs in CD4+ T cells from individuals with latent tuberculosis versus active tuberculosis.

    PubMed

    Fu, Yurong; Yi, Zhengjun; Li, Jianhua; Li, Ruifang

    2014-03-01

    The mechanisms of latent tuberculosis (TB) infection remain elusive. Roles of microRNA (miRNA) have been highlighted in pathogen-host interactions recently. To identify miRNAs involved in the immune response to TB, expression profiles of miRNAs in CD4(+) T cells from patients with latent TB, active TB and healthy controls were investigated by microarray assay and validated by RT-qPCR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyse the significant functions and involvement in signalling pathways of the differentially expressed miRNAs. To identify potential target genes for miR-29, interferon-γ (IFN-γ) mRNA expression was measured by RT-qPCR. Our results showed that 27 miRNAs were deregulated among the three groups. RT-qPCR results were generally consistent with the microarray data. We observed an inverse correlation between miR-29 level and IFN-γ mRNA expression in CD4(+) T cells. GO and KEGG pathway analysis showed that the possible target genes of deregulated miRNAs were significantly enriched in mitogen-activated protein kinase signalling pathway, focal adhesion and extracellular matrix receptor interaction, which might be involved in the transition from latent to active TB. In all, for the first time, our study revealed that some miRNAs in CD4(+) T cells were altered in latent and active TB. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in TB. The study might help to improve understanding of the relationship between miRNAs in CD4(+) T cells and TB, and laid an important foundation for further identification of the underlying mechanisms of latent TB infection and its reactivation.

  16. Competition and deregulation in the electric industry. A study of organizational change: The New York State Public Service Commission

    NASA Astrophysics Data System (ADS)

    Ashley, Deborah J. Cordaro

    2000-11-01

    Public organizations are formed in response to societal needs. They collect taxes, educate children, enforce laws and provide protection to the environment, the nation and consumers. One such organization is the New York State Public Service Commission. In 1907, legislation was passed to form the New York State Public Service Commission the first regulatory body of its kind in the United States. Its mission was to provide safe, reliable and reasonably priced electricity. Subsequently, this became the model that was implemented in every state in the nation. The past decade heralds an era of competition and a lessening of regulatory control. The telephone, natural gas and airline industries are in various stages of deregulation, and the electric industry is beginning down this path as well. In an environment such as this, are regulatory organizations necessary, and if they are, how can they organize to meet the new societal requirements? The case of the New York State Public Service Commission at this point in time offers a real time study of a regulatory body immersed in an environment that is calling for competition and an end to big government. Utilizing case studies of industries that have deregulated, or are in the process of deregulating, indicates a future societal need for regulations. This result does not lead to a conclusion that organizational change is unnecessary. This Dissertation will lay out the current organizational structure of the Public Service Commission, give an overview of the environmental signals, describe the mission/core values, and illustrate general political and employee factors that are indigenous to public service. Utilizing both classic and current organizational theory, an evaluation will be made of the Commission's need for change, their ability to change, and obstacles they may encounter.

  17. Federal participation in LEED

    SciTech Connect

    Payne, Christopher; Dyer, Beverly

    2004-11-10

    The federal government has been an active participant in the development and use of USGBC's Leadership in Energy & Environmental Design Green Building Rating System (LEED). This paper presents a review of this participation and some expectations for ongoing partnership.

  18. Federal Internship Improvement Act

    THOMAS, 112th Congress

    Rep. Connolly, Gerald E. [D-VA-11

    2011-03-03

    03/18/2011 Referred to the Subcommittee on Federal Workforce, U.S. Postal Service, and Labor Policy. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  19. 78 FR 27968 - Federal Management Regulation; Redesignations of Federal Buildings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-13

    ... redesignated buildings are as follows: Former Name New Name Ariel Rios Federal Building William Jefferson... Midland, TX 79701 Federal Office Building 8 Thomas P. O'Neill, Jr., Federal Building 200 C Street, SW....

  20. Federal Guidance for Radiation Protection

    EPA Pesticide Factsheets

    EPA produces federal guidance technical reports, which standardize dose and risk assessment and issues radiation protection guidance to federal agencies. This page provides links to federal guidance policy recommendations and technical reports.

  1. Deregulation of Hepatic Insulin Sensitivity Induced by Central Lipid Infusion in Rats Is Mediated by Nitric Oxide

    PubMed Central

    Marsollier, Nicolas; Kassis, Nadim; Mezghenna, Karima; Soty, Maud; Fioramonti, Xavier; Lacombe, Amélie; Joly, Aurélie; Pillot, Bruno; Zitoun, Carine; Vilar, José; Mithieux, Gilles; Gross, René; Lajoix, Anne-Dominique; Routh, Vanessa; Magnan, Christophe; Cruciani-Guglielmacci, Céline

    2009-01-01

    Background Deregulation of hypothalamic fatty acid sensing lead to hepatic insulin-resistance which may partly contribute to further impairment of glucose homeostasis. Methodology We investigated here whether hypothalamic nitric oxide (NO) could mediate deleterious peripheral effect of central lipid overload. Thus we infused rats for 24 hours into carotid artery towards brain, either with heparinized triglyceride emulsion (Intralipid, IL) or heparinized saline (control rats). Principal Findings Lipids infusion led to hepatic insulin-resistance partly related to a decreased parasympathetic activity in the liver assessed by an increased acetylcholinesterase activity. Hypothalamic nitric oxide synthases (NOS) activities were significantly increased in IL rats, as the catalytically active neuronal NOS (nNOS) dimers compared to controls. This was related to a decrease in expression of protein inhibitor of nNOS (PIN). Effect of IL infusion on deregulated hepatic insulin-sensitivity was reversed by carotid injection of non selective NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) and also by a selective inhibitor of the nNOS isoform, 7-Nitro-Indazole (7-Ni). In addition, NO donor injection (L-arginine and SNP) within carotid in control rats mimicked lipid effects onto impaired hepatic insulin sensitivity. In parallel we showed that cultured VMH neurons produce NO in response to fatty acid (oleic acid). Conclusions/Significance We conclude that cerebral fatty acid overload induces an enhancement of nNOS activity within hypothalamus which is, at least in part, responsible fatty acid increased hepatic glucose production. PMID:19680547

  2. Deregulated expression of Cdc6 in the skin facilitates papilloma formation and affects the hair growth cycle

    PubMed Central

    Búa, Sabela; Sotiropoulou, Peggy; Sgarlata, Cecilia; Borlado, Luis R; Eguren, Manuel; Domínguez, Orlando; Ortega, Sagrario; Malumbres, Marcos; Blanpain, Cedric; Méndez, Juan

    2015-01-01

    Cdc6 encodes a key protein for DNA replication, responsible for the recruitment of the MCM helicase to replication origins during the G1 phase of the cell division cycle. The oncogenic potential of deregulated Cdc6 expression has been inferred from cellular studies, but no mouse models have been described to study its effects in mammalian tissues. Here we report the generation of K5-Cdc6, a transgenic mouse strain in which Cdc6 expression is deregulated in tissues with stratified epithelia. Higher levels of CDC6 protein enhanced the loading of MCM complexes to DNA in epidermal keratinocytes, without affecting their proliferation rate or inducing DNA damage. While Cdc6 overexpression did not promote skin tumors, it facilitated the formation of papillomas in cooperation with mutagenic agents such as DMBA. In addition, the elevated levels of CDC6 protein in the skin extended the resting stage of the hair growth cycle, leading to better fur preservation in older mice. PMID:26697840

  3. Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells

    SciTech Connect

    Martinotti, Simona; Ranzato, Elia; Parodi, Monica; Vitale, Massimo; Burlando, Bruno

    2014-01-01

    Malignant mesothelioma (MMe) is a poor-prognosis tumor in need of innovative therapies. In a previous in vivo study, we showed synergistic anti-MMe properties of the ascorbate/epigallocatechin-3-gallate/gemcitabine combination. We have now focused on the mechanism of action, showing the induction of apoptosis and cell cycle arrest through measurements of caspase 3, intracellular Ca{sup 2+}, annexin V, and DNA content. StellArray™ PCR technology and Western immunoblotting revealed DAPK2-dependent apoptosis, upregulation of cell cycle promoters, downregulation of cell cycle checkpoints and repression of NFκB expression. The complex of data indicates that the mixture is synergistic in inducing cell cycle deregulation and non-inflammatory apoptosis, suggesting its possible use in MMe treatment. - Highlights: • Ascorbate/epigallocathechin-gallate/gemcitabine has been tested on mesothelioma cells • A synergistic mechanism has been shown for cell cycle arrest and apoptosis • PCR-array analysis has revealed the de-regulation of apoptosis and cell cycle genes • Maximum upregulation has been found for the Death-Associated Protein Kinase-2 gene • Data suggest that the mixture could be used as a clinical treatment.

  4. Metabolomics and In-Silico Analysis Reveal Critical Energy Deregulations in Animal Models of Parkinson’s Disease

    PubMed Central

    Poliquin, Pierre O.; Chen, Jingkui; Cloutier, Mathieu; Trudeau, Louis-Éric; Jolicoeur, Mario

    2013-01-01

    Parkinson’s disease (PD) is a multifactorial disease known to result from a variety of factors. Although age is the principal risk factor, other etiological mechanisms have been identified, including gene mutations and exposure to toxins. Deregulation of energy metabolism, mostly through the loss of complex I efficiency, is involved in disease progression in both the genetic and sporadic forms of the disease. In this study, we investigated energy deregulation in the cerebral tissue of animal models (genetic and toxin induced) of PD using an approach that combines metabolomics and mathematical modelling. In a first step, quantitative measurements of energy-related metabolites in mouse brain slices revealed most affected pathways. A genetic model of PD, the Park2 knockout, was compared to the effect of CCCP, a complex I blocker. Model simulated and experimental results revealed a significant and sustained decrease in ATP after CCCP exposure, but not in the genetic mice model. In support to data analysis, a mathematical model of the relevant metabolic pathways was developed and calibrated onto experimental data. In this work, we show that a short-term stress response in nucleotide scavenging is most probably induced by the toxin exposure. In turn, the robustness of energy-related pathways in the model explains how genetic perturbations, at least in young animals, are not sufficient to induce significant changes at the metabolite level. PMID:23935941

  5. Deregulated chlorophyll b synthesis reduces the energy transfer rate between photosynthetic pigments and induces photodamage in Arabidopsis thaliana.

    PubMed

    Sakuraba, Yasuhito; Yokono, Makio; Akimoto, Seiji; Tanaka, Ryouichi; Tanaka, Ayumi

    2010-06-01

    Chl b is one of the major light-harvesting pigments in land plants. The synthesis of Chl b is strictly regulated in response to light conditions in order to control the antenna size of photosystems. Regulation of Chl b also affects its distribution as it occurs preferentially in the peripheral antenna complexes. However, it has not been experimentally shown how plants respond to environmental conditions when they accumulate excess Chl b. Previously, we produced an Arabidopsis transgenic plant (referred to as the BC plant) in which Chl b biosynthesis was enhanced. In this study, we analyzed the photosynthetic properties and genome-wide gene expression in this plant under high light conditions in order to understand the effects of deregulated Chl b biosynthesis. The energy transfer rates between Chl a molecules in PSII decreased and H(2)O(2) accumulated extensively in the BC plant. Microarray analysis revealed that a group of genes involved in anthocyanin biosynthesis was down-regulated and that another group of genes, reported to be sensitive to H(2)O(2), was up-regulated in the BC plant. We also found that anthocyanin levels were low, which was consistent with the results of the microarray analysis. These results indicate that deregulation of Chl b caused severe photodamage and altered gene expression profiles under strong illumination. The importance of the regulation of Chl b synthesis is discussed in relation to the correct localization of Chl b and gene expression.

  6. Investigation of deregulated genes of Notch signaling pathway in human T cell acute lymphoblastic leukemia cell lines and clinical samples.

    PubMed

    Paryan, Mahdi; Mohammadi-Yeganeh, Samira; Samiee, Siamak Mirab; Soleimani, Masoud; Arefian, Ehsan; Azadmanesh, Keyhan; Poopak, Behzad; Mostafavi, Ehsan; Karimipoor, Morteza; Mahdian, Reza

    2013-10-01

    In diagnostic research challenges, quantitative real-time PCR (QPCR) has been widely utilized in gene expression analysis because of its sensitivity, accuracy, reproducibility, and most importantly, quantitativeness. Real-time PCR base kits are wildly applicable in cancer signaling pathways, especially in cancer investigations. T-cell acute lymphoblastic leukemia (T-ALL) is a type of leukemia that is more common in older children and teenagers. Deregulation of the Notch signaling pathway promotes proliferation and inhibits apoptosis of the lymphoblastic T cells. The aim of this study was to investigate the effect of Notch signaling activation on the expression of target genes using real-time QPCR and further use this method in clinical examination after validation. Two T-ALL cell lines, Jurkat and Molt-4, were used as models for activation of the Notch signaling via over-expression of the Notch1 intracellular domain. Expression analysis was performed for six downstream target genes (NCSTN, APH1, PSEN1, ADAM17, NOTCH1 and C-MYC) which play critical roles in the Notch signaling pathway. The results showed significant difference in the expression of target genes in the deregulated Notch signaling pathway. These results were also verified in 12 clinical samples bearing over-expression of the Notch signaling pathway. Identification of such downstream Notch target genes, which have not been studied inclusively, provides insights into the mechanisms of the Notch function in T cell leukemia, and may help identify novel diagnoses and therapeutic targets in acute lymphoblastic leukemia.

  7. Amyloid beta deregulates astroglial mGluR5-mediated calcium signaling via calcineurin and Nf-kB.

    PubMed

    Lim, Dmitry; Iyer, Anand; Ronco, Virginia; Grolla, Ambra A; Canonico, Pier Luigi; Aronica, Eleonora; Genazzani, Armando A

    2013-07-01

    The amyloid hypothesis of Alzheimer's disease (AD) suggests that soluble amyloid β (Aβ) is an initiator of a cascade of events eventually leading to neurodegeneration. Recently, we reported that Aβ deranged Ca(2+) homeostasis specifically in hippocampal astrocytes by targeting key elements of Ca(2+) signaling, such as mGluR5 and IP3 R1. In the present study, we dissect a cascade of signaling events by which Aβ deregulates glial Ca(2+) : (i) 100 nM Aβ leads to an increase in cytosolic calcium after 4-6 h of treatment; (ii) mGluR5 is increased after 24 h of treatment; (iii) this increase is blocked by inhibitors of calcineurin (CaN) and NF-kB. Furthermore, we show that Aβ treatment of glial cells leads to de-phosphorylation of Bcl10 and an increased CaN-Bcl10 interaction. Last, mGluR5 staining is augmented in hippocampal astrocytes of AD patients in proximity of Aβ plaques and co-localizes with nuclear accumulation of the p65 NF-kB subunit and increased staining of CaNAα. Taken together our data suggest that nanomolar [Aβ] deregulates Ca(2+) homeostasis via CaN and its downstream target NF-kB, possibly via the cross-talk of Bcl10 in hippocampal astrocytes.

  8. Advanced Gas Turbine (AGT) Technology Project

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Technical work on the design and effort leading to the testing of a 74.5 kW (100 hp) automotive gas turbine engine is reviewed. Development of the engine compressor, gasifier turbine, power turbine, combustor, regenerator, and secondary system is discussed. Ceramic materials development and the application of such materials in the gas turbine engine components is described.

  9. Advanced Gas Turbine (AGT) powertrain system

    NASA Technical Reports Server (NTRS)

    Helms, H. E.; Kaufeld, J.; Kordes, R.

    1981-01-01

    A 74.5 kW(100 hp) advanced automotive gas turbine engine is described. A design iteration to improve the weight and production cost associated with the original concept is discussed. Major rig tests included 15 hours of compressor testing to 80% design speed and the results are presented. Approximately 150 hours of cold flow testing showed duct loss to be less than the design goal. Combustor test results are presented for initial checkout tests. Turbine design and rig fabrication is discussed. From a materials study of six methods to fabricate rotors, two have been selected for further effort. A discussion of all six methods is given.

  10. Advanced Gas Turbine (AGT) technology development

    NASA Technical Reports Server (NTRS)

    1983-01-01

    A 74.5 kW (100 hp) automotive gas turbine was evaluated. The engine structure, bearings, oil system, and electronics were demonstrated and no shaft dynamics or other vibration problem were encountered. Areas identified during the five tests are the scroll retention features, and transient thermal deflection of turbine backplates. Modifications were designed. Seroll retention is addressed by modifying the seal arrangement in front of the gasifier turbine assembly, which will increase the pressure load on the scroll in the forward direction and thereby increase the retention forces. the backplate thermal deflection is addressed by geometric changes and thermal insulation to reduce heat input. Combustor rig proof testing of two ceramic combustor assemblies was completed. The combustor was modified to incorporate slots and reduce sharp edges, which should reduce thermal stresses. The development work focused on techniques to sinter these barrier materials onto the ceramic rotors with successes for both material systems. Silicon carbide structural parts, including engine configuration gasifier rotors (ECRs), preliminary gasifier scroll parts, and gasifier and power turbine vanes are fabricated.

  11. A Primer on Electric Utilities, Deregulation, and Restructuring of U.S. Electricity Markets

    SciTech Connect

    Warwick, William M.

    2002-06-03

    This primer is offered as an introduction to utility restructuring to better prepare readers for ongoing changes in public utilities and associated energy markets. It is written for use by individuals with responsibility for the management of facilities that use energy, including energy managers, procurement staff, and managers with responsibility for facility operations and budgets. The primer was prepared by the Pacific Northwest National Laboratory under sponsorship from the U.S. Department of Energy?s Federal Energy Management Program. The impetus for this primer originally came from the Government Services Administration who supported its initial development.

  12. Rural Education: The Federal Response.

    ERIC Educational Resources Information Center

    Hearn, Norman E.

    1981-01-01

    Reviews federal efforts to develop a rural education federal agenda, five basic problems of rural areas which lend themselves to federal solutions, Department of Education proposals for fiscal year 1982, significant federal responses/already in progress, and strengths and advantages of rural schools. (AN)

  13. Federal Forecasters Directory, 1995.

    ERIC Educational Resources Information Center

    National Center for Education Statistics (ED), Washington, DC.

    This directory lists employees of the federal government who are involved in forecasting for policy formation and trend prediction purposes. Job title, agency, business address, phone or e-mail number, and specialty areas are listed for each employee. Employees are listed for the following agencies: (1) Bureau of the Census; (2) Bureau of Economic…

  14. Federal-State Relationships.

    ERIC Educational Resources Information Center

    Bystrom, John

    The Federal Communications Commission in 1938 set aside AM radio assignments for future educational stations. In the 1960's it made additional assignments for education: long-range FM radio, multiplex sub-carrier channels; and UHF, VHF, and Instructional Television Fixed Service channels for statewide ETV broadcast service. Such networks aid the…

  15. Federal Regulation of Education.

    ERIC Educational Resources Information Center

    Shapiro, Martin

    Fresh light might be shed on problems of federal education policy by treating them not only as problems of intergovernmental relations but of government regulation of enterprise, given that they involve the attempts of a central government to influence the conduct of enterprises that it does not own nor directly operate. Using well-established…

  16. Defensive Federal Litigation

    DTIC Science & Technology

    2007-11-02

    of Substantive Rights .... 4-15 ( b ) Back Pay Claim s ................................................................ 4- 23 (c) O ther Issues...3): V enue ......................................................................... 2-26 d . Rule 12( b )(7): Indispensable Parties...Federal Tort Claim s A ct ....................................................... 4-7 ( d ) O ther Statutes

  17. An integrated genome-wide approach to discover deregulated microRNAs in non-small cell lung cancer: Clinical significance of miR-23b-3p deregulation.

    PubMed

    Begum, Shahnaz; Hayashi, Masamichi; Ogawa, Takenori; Jabboure, Fayez J; Brait, Mariana; Izumchenko, Evgeny; Tabak, Sarit; Ahrendt, Steven A; Westra, William H; Koch, Wayne; Sidransky, David; Hoque, Mohammad O

    2015-08-28

    In spite of significant technical advances, genesis and progression of non-small cell lung cancer (NSCLC) remain poorly understood. We undertook an integrated genetic approach to discover novel microRNAs that were deregulated in NSCLCs. A total 119 primary NSCLCs with matched normal were analyzed for genome-wide copy number changes. We also tested a subset of matched samples by microRNA expression array, and integrated them to identify microRNAs positioned in allelic imbalance area. Our findings support that most of the identified deregulated microRNAs (miR-21, miR-23b, miR-31, miR-126, miR-150, and miR-205) were positioned in allelic imbalance areas. Among microRNAs tested in independent 114 NSCLCs, overexpression of miR-23b was revealed to be a significantly poor prognostic factor of recurrence free survival (HR = 2.40, P = 0.005, 95%CI: 1.32-4.29) and overall survival (HR = 2.35, P = 0.005, 95%CI: 1.30-4.19) in multivariable analysis. In addition, overexpression of miR-23b in H1838 cell line significantly increased cell proliferation, while inhibition of miR-23b in H1437 and H1944 cell lines significantly decreased cell doubling time. In summary, integration of genomic analysis and microRNA expression profiling could identify novel cancer-related microRNAs, and miR-23b could be a potential prognostic marker for early stage NSCLCs. Further biological studies of miR-23b are warranted for the potential development of targeted therapy.

  18. An integrated genome-wide approach to discover deregulated microRNAs in non-small cell lung cancer: Clinical significance of miR-23b-3p deregulation

    PubMed Central

    Begum, Shahnaz; Hayashi, Masamichi; Ogawa, Takenori; Jabboure, Fayez J.; Brait, Mariana; Izumchenko, Evgeny; Tabak, Sarit; Ahrendt, Steven A.; Westra, William H.; Koch, Wayne; Sidransky, David; Hoque, Mohammad O.

    2015-01-01

    In spite of significant technical advances, genesis and progression of non-small cell lung cancer (NSCLC) remain poorly understood. We undertook an integrated genetic approach to discover novel microRNAs that were deregulated in NSCLCs. A total 119 primary NSCLCs with matched normal were analyzed for genome-wide copy number changes. We also tested a subset of matched samples by microRNA expression array, and integrated them to identify microRNAs positioned in allelic imbalance area. Our findings support that most of the identified deregulated microRNAs (miR-21, miR-23b, miR-31, miR-126, miR-150, and miR-205) were positioned in allelic imbalance areas. Among microRNAs tested in independent 114 NSCLCs, overexpression of miR-23b was revealed to be a significantly poor prognostic factor of recurrence free survival (HR = 2.40, P = 0.005, 95%CI: 1.32–4.29) and overall survival (HR = 2.35, P = 0.005, 95%CI: 1.30–4.19) in multivariable analysis. In addition, overexpression of miR-23b in H1838 cell line significantly increased cell proliferation, while inhibition of miR-23b in H1437 and H1944 cell lines significantly decreased cell doubling time. In summary, integration of genomic analysis and microRNA expression profiling could identify novel cancer-related microRNAs, and miR-23b could be a potential prognostic marker for early stage NSCLCs. Further biological studies of miR-23b are warranted for the potential development of targeted therapy. PMID:26314549

  19. Deregulated proteolysis by the F-box proteins SKP2 and β-TrCP: tipping the scales of cancer

    PubMed Central

    Frescas, David; Pagano, Michele

    2009-01-01

    The maintenance and preservation of distinct phases during the cell cycle is a highly complex and coordinated process. It is regulated by phosphorylation — through the activity of cyclin-dependent kinases (CDKs) — and protein degradation, which occurs through ubiquitin ligases such as SCF (SKP1–CUL1–F-box protein) complexes and APC/C (anaphase-promoting complex/cyclosome). Here, we explore the functionality and biology of the F-box proteins, SKP2 (S-phase kinase-associated protein 2) and β-TrCP (β-transducin repeat-containing protein), which are emerging as important players in cancer biogenesis owing to the deregulated proteolysis of their substrates. PMID:18500245

  20. Enhancer Sequence Variants and Transcription Factor Deregulation Synergize to Construct Pathogenic Regulatory Circuits in B Cell Lymphoma

    PubMed Central

    Koues, Olivia I.; Kowalewski, Rodney A.; Chang, Li-Wei; Pyfrom, Sarah C.; Schmidt, Jennifer A.; Luo, Hong; Sandoval, Luis E.; Hughes, Tyler B.; Bednarski, Jeffrey J.; Cashen, Amanda F.; Payton, Jacqueline E.; Oltz, Eugene M.

    2014-01-01

    Summary Most B cell lymphomas arise in the germinal center (GC), where humoral immune responses evolve from potentially oncogenic cycles of mutation, proliferation, and clonal selection. Although lymphoma gene expression diverges significantly from GC-B cells, underlying mechanisms that alter the activities of corresponding regulatory elements (REs) remain elusive. Here we define the complete pathogenic circuitry of human follicular lymphoma (FL), which activates or decommissions REs from normal GC-B cells and commandeers enhancers from other lineages. Moreover, independent sets of transcription factors, whose expression was deregulated in FL, targeted commandeered versus decommissioned REs. Our approach revealed two distinct subtypes of low-grade FL, whose pathogenic circuitries resembled GC-B or activated B cells. FL-altered enhancers also were enriched for sequence variants, including somatic mutations, which disrupt transcription factor binding and expression of circuit-linked genes. Thus, the pathogenic regulatory circuitry of FL reveals distinct genetic and epigenetic etiologies for GC-B transformation. PMID:25607463

  1. Integrative identification of deregulated miRNA/TF-mediated gene regulatory loops and networks in prostate cancer.

    PubMed

    Afshar, Ali Sobhi; Xu, Joseph; Goutsias, John

    2014-01-01

    MicroRNAs (miRNAs) have attracted a great deal of attention in biology and medicine. It has been hypothesized that miRNAs interact with transcription factors (TFs) in a coordinated fashion to play key roles in regulating signaling and transcriptional pathways and in achieving robust gene regulation. Here, we propose a novel integrative computational method to infer certain types of deregulated miRNA-mediated regulatory circuits at the transcriptional, post-transcriptional and signaling levels. To reliably predict miRNA-target interactions from mRNA/miRNA expression data, our method collectively utilizes sequence-based miRNA-target predictions obtained from several algorithms, known information about mRNA and miRNA targets of TFs available in existing databases, certain molecular structures identified to be statistically over-represented in gene regulatory networks, available molecular subtyping information, and state-of-the-art statistical techniques to appropriately constrain the underlying analysis. In this way, the method exploits almost every aspect of extractable information in the expression data. We apply our procedure on mRNA/miRNA expression data from prostate tumor and normal samples and detect numerous known and novel miRNA-mediated deregulated loops and networks in prostate cancer. We also demonstrate instances of the results in a number of distinct biological settings, which are known to play crucial roles in prostate and other types of cancer. Our findings show that the proposed computational method can be used to effectively achieve notable insights into the poorly understood molecular mechanisms of miRNA-mediated interactions and dissect their functional roles in cancer in an effort to pave the way for miRNA-based therapeutics in clinical settings.

  2. Integrative Identification of Deregulated MiRNA/TF-Mediated Gene Regulatory Loops and Networks in Prostate Cancer

    PubMed Central

    Afshar, Ali Sobhi; Xu, Joseph; Goutsias, John

    2014-01-01

    MicroRNAs (miRNAs) have attracted a great deal of attention in biology and medicine. It has been hypothesized that miRNAs interact with transcription factors (TFs) in a coordinated fashion to play key roles in regulating signaling and transcriptional pathways and in achieving robust gene regulation. Here, we propose a novel integrative computational method to infer certain types of deregulated miRNA-mediated regulatory circuits at the transcriptional, post-transcriptional and signaling levels. To reliably predict miRNA-target interactions from mRNA/miRNA expression data, our method collectively utilizes sequence-based miRNA-target predictions obtained from several algorithms, known information about mRNA and miRNA targets of TFs available in existing databases, certain molecular structures identified to be statistically over-represented in gene regulatory networks, available molecular subtyping information, and state-of-the-art statistical techniques to appropriately constrain the underlying analysis. In this way, the method exploits almost every aspect of extractable information in the expression data. We apply our procedure on mRNA/miRNA expression data from prostate tumor and normal samples and detect numerous known and novel miRNA-mediated deregulated loops and networks in prostate cancer. We also demonstrate instances of the results in a number of distinct biological settings, which are known to play crucial roles in prostate and other types of cancer. Our findings show that the proposed computational method can be used to effectively achieve notable insights into the poorly understood molecular mechanisms of miRNA-mediated interactions and dissect their functional roles in cancer in an effort to pave the way for miRNA-based therapeutics in clinical settings. PMID:24968068

  3. MiR-9, -31, and -182 deregulation promote proliferation and tumor cell survival in colon cancer.

    PubMed

    Cekaite, Lina; Rantala, Juha K; Bruun, Jarle; Guriby, Marianne; Agesen, Trude H; Danielsen, Stine A; Lind, Guro E; Nesbakken, Arild; Kallioniemi, Olli; Lothe, Ragnhild A; Skotheim, Rolf I

    2012-09-01

    Several microRNAs (miRNAs) are known to be deregulated in colon cancer, but the mechanisms behind their potential involvement on proliferation and tumor cell survival are unclear. The present study aimed to identify miRNAs with functional implications for development of colon cancer. The cell proliferation and apoptosis were examined following perturbations of miRNA levels by employing a comprehensive miRNA library screen. miRNAs nominated for relevance to colon cancer were validated on expression and functional levels. By integrating the effect of miRNA up-regulation with the endogenous miRNA expression levels within the HT29, HCT116, and SW480 colon cancer cell lines, we identified miRNAs controlling cell proliferation (n = 53) and apoptosis (n = 93). From these functionally nominated miRNAs, we narrowed the list to 10 oncogene- and 20 tumor suppressor-like miRNAs that were also differentially expressed between colon cancer (n = 80) and normal colonic mucosa (n = 20). The differential expressions of miR-9, miR-31, and miR-182 were successfully validated in a series of colon carcinomas (n = 30) and polyps (n = 10) versus normal colonic mucosa (n = 10), whereas the functional effect was confirmed in an in-depth validation using different cell viability and apoptotic markers. Several transcription factors and genes regulating cell proliferation were identified as putative target genes by integrative miRNA/mRNA expression analysis obtained from the same colon cancer patient samples. This study suggests that deregulated expression of miR-9, miR-31, and miR-182 during carcinogenesis plays a significant role in the development of colon cancer by promoting proliferation and tumor cell survival.

  4. Linking deregulation of non-coding RNA to the core pathophysiology of Alzheimer's disease: an integrative review.

    PubMed

    Millan, Mark J

    2017-03-17

    The human genome encodes a vast repertoire of protein non-coding RNAs (ncRNA), some specific to the brain. MicroRNAs, which interfere with the translation of target mRNAs, are of particular interest since their deregulation has been implicated in neurodegenerative disorders like Alzheimer's disease (AD). However, it remains challenging to link the complex body of observations on miRNAs and AD into a coherent framework. Using extensive graphical support, this article discusses how a diverse panoply of miRNAs convergently and divergently impact (and are impacted by) core pathophysiological processes underlying AD: neuroinflammation and oxidative stress; aberrant generation of β-amyloid-42 (Aβ42); anomalies in the production, cleavage and post-translational marking of Tau; impaired clearance of Aβ42 and Tau; perturbation of axonal organisation; disruption of synaptic plasticity; endoplasmic reticulum stress and the unfolded protein response; mitochondrial dysfunction; aberrant induction of cell cycle re-entry; and apoptotic loss of neurons. Intriguingly, some classes of miRNA provoke these cellular anomalies, whereas others act in a counter-regulatory, protective mode. Moreover, changes in levels of certain species of miRNA are a consequence of the above-mentioned anomalies. In addition to miRNAs, circular RNAs, piwiRNAs, long non-coding RNAs and other types of ncRNA are being increasingly implicated in AD. Overall, a complex mesh of deregulated and multi-tasking ncRNAs reciprocally interacts with pathophysiological mechanisms underlying AD. Alterations in ncRNAs can be detected in CSF and the circulation as well as the brain, and are showing promise as biomarkers, with the ultimate goal clinical exploitation as targets for novel modes of symptomatic and course-altering therapy.

  5. Needle Federated Search Engine

    SciTech Connect

    2009-12-01

    The Idaho National Laboratory (INL) has combined a number of technologies, tools, and resources to accomplish a new means of federating search results. The resulting product is a search engine called Needle, an open-source-based tool that the INL uses internally for researching across a wide variety of information repositories. Needle has a flexible search interface that allows end users to point at any available data source. A user can select multiple sources such as commercial databases (Web of Science, Engineering Index), external resources (WorldCat, Google Scholar), and internal corporate resources (email, document management system, library collections) in a single interface with one search query. In the future, INL hopes to offer this open-source engine to the public. This session will outline the development processes for making Needle™s search interface and simplifying the federation of internal and external data sources.

  6. Federal Interagency Geothermal Activities

    SciTech Connect

    Anderson, Arlene; Prencipe, Loretta; Todaro, Richard M.; Cuyler, David; Eide, Elizabeth

    2011-06-01

    This collaborative document describes the roles and responsibilities of key Federal agencies in the development of geothermal technologies including the U.S. Department of Energy (DOE); the U.S. Department of Agriculture (USDA), including the U.S. Forest Service; the U.S. Department of Interior (DOI), including the United States Geological Survey (USGS) and Bureau of Land Management (BLM); the Environmental Protection Agency (EPA); and the Department of Defense (DOD).

  7. Indochina: The Federation Factor.

    DTIC Science & Technology

    1982-12-01

    alliances unite territorial units to form "communities" or "blocs", or confederations. Other usual features of modern alliances are: 1. They are...Revolution in Modern Vietnam. Boston: Houghton Mifflin Co., 1976. Woodside, Alexander B., Vietnam and the Chinese Model: A Comparative Study of Nguyen and...of an Indo- chinese Federation. While a trend toward greater regional associations has been observed - both historically and during the recent past

  8. Federating Metadata Catalogs

    NASA Astrophysics Data System (ADS)

    Baru, C.; Lin, K.

    2009-04-01

    The Geosciences Network project (www.geongrid.org) has been developing cyberinfrastructure for data sharing in the Earth Science community based on a service-oriented architecture. The project defines a standard "software stack", which includes a standardized set of software modules and corresponding service interfaces. The system employs Grid certificates for distributed user authentication. The GEON Portal provides online access to these services via a set of portlets. This service-oriented approach has enabled the GEON network to easily expand to new sites and deploy the same infrastructure in new projects. To facilitate interoperation with other distributed geoinformatics environments, service standards are being defined and implemented for catalog services and federated search across distributed catalogs. The need arises because there may be multiple metadata catalogs in a distributed system, for example, for each institution, agency, geographic region, and/or country. Ideally, a geoinformatics user should be able to search across all such catalogs by making a single search request. In this paper, we describe our implementation for such a search capability across federated metadata catalogs in the GEON service-oriented architecture. The GEON catalog can be searched using spatial, temporal, and other metadata-based search criteria. The search can be invoked as a Web service and, thus, can be imbedded in any software application. The need for federated catalogs in GEON arises because, (i) GEON collaborators at the University of Hyderabad, India have deployed their own catalog, as part of the iGEON-India effort, to register information about local resources for broader access across the network, (ii) GEON collaborators in the GEO Grid (Global Earth Observations Grid) project at AIST, Japan have implemented a catalog for their ASTER data products, and (iii) we have recently deployed a search service to access all data products from the EarthScope project in the US

  9. Deregulated miRNAs in Hereditary Breast Cancer Revealed a Role for miR-30c in Regulating KRAS Oncogene

    PubMed Central

    Tanic, Miljana; Yanowsky, Kira; Rodriguez-Antona, Cristina; Andrés, Raquel; Márquez-Rodas, Iván; Osorio, Ana; Benitez, Javier; Martinez-Delgado, Beatriz

    2012-01-01

    Aberrant miRNA expression has been previously established in breast cancer and has clinical relevance. However, no studies so far have defined miRNAs deregulated in hereditary breast tumors. In this study we investigated the role of miRNAs in hereditary breast tumors comparing with normal breast tissue. Global miRNA expression profiling using Exiqon microarrays was performed on 22 hereditary breast tumors and 15 non-tumoral breast tissues. We identified 19 miRNAs differentially expressed, most of them down-regulated in tumors. An important proportion of deregulated miRNAs in hereditary tumors were previously identified commonly deregulated in sporadic breast tumors. Under-expression of these miRNAs was validated by qRT-PCR in additional 18 sporadic breast tumors and their normal breast tissue counterparts. Pathway enrichment analysis revealed that deregulated miRNAs collectively targeted a number of genes belonging to signaling pathways such as MAPK, ErbB, mTOR, and those regulating cell motility or adhesion. In silico prediction detected KRAS oncogene as target of several deregulated miRNAs. In particular, we experimentally validated KRAS as a miR-30c target. Luciferase assays confirmed that miR-30c binds the 3′UTR of KRAS transcripts and expression of pre-miR-30c down-regulated KRAS mRNA and protein. Furthermore, miR-30c overexpression inhibited proliferation of breast cancer cells. Our results identify miRNAs associated to hereditary breast cancer, as well as miRNAs commonly miss-expressed in hereditary and sporadic tumors, suggesting common underlying mechanisms of tumor progression. In addition, we provide evidence that KRAS is a target of miR-30c, and that this miRNA suppresses breast cancer cell growth potentially through inhibition of KRAS signaling. PMID:22701724

  10. Assisted Living Federation of America

    MedlinePlus

    ... Logos Membership FAQs Advocacy Advocacy Top Trending Issues Silver PAC Federal Public Policy State Regulations and Licensing ... Argentum Member Pledge Advocacy Advocacy Top Trending Issues Silver PAC Argentum Advocates Cobb Cup Federal Public Policy ...

  11. Eliminating the Federal Thrift Charter

    DTIC Science & Technology

    1997-06-01

    FDIC), the Office of the Comptroller of the Currency (OCC), the Federal Reserve , and the Office of Thrift Supervision (OTS). (See Table 1 for a list...the FDIC is the primary federal regulator for state-chartered commercial banks that are not members of the Federal Reserve System. It is also the...commercial bank regulators are the Office of the Comptroller of the Currency and the Federal Reserve . The OCC, established in 1863 by the National Currency

  12. An Xrootd Italian Federation

    NASA Astrophysics Data System (ADS)

    Boccali, T.; Donvito, G.; Diacono, D.; Marzulli, G.; Pompili, A.; Della Ricca, G.; Mazzoni, E.; Argiro, S.; Gregori, D.; Grandi, C.; Bonacorsi, D.; Lista, L.; Fabozzi, F.; Barone, L. M.; Santocchia, A.; Riahi, H.; Tricomi, A.; Sgaravatto, M.; Maron, G.

    2014-06-01

    The Italian community in CMS has built a geographically distributed network in which all the data stored in the Italian region are available to all the users for their everyday work. This activity involves at different level all the CMS centers: the Tier1 at CNAF, all the four Tier2s (Bari, Rome, Legnaro and Pisa), and few Tier3s (Trieste, Perugia, Torino, Catania, Napoli, ...). The federation uses the new network connections as provided by GARR, our NREN (National Research and Education Network), which provides a minimum of 10 Gbit/s to all the sites via the GARR-X[2] project. The federation is currently based on Xrootd[1] technology, and on a Redirector aimed to seamlessly connect all the sites, giving the logical view of a single entity. A special configuration has been put in place for the Tier1, CNAF, where ad-hoc Xrootd changes have been implemented in order to protect the tape system from excessive stress, by not allowing WAN connections to access tape only files, on a file-by-file basis. In order to improve the overall performance while reading files, both in terms of bandwidth and latency, a hierarchy of xrootd redirectors has been implemented. The solution implemented provides a dedicated Redirector where all the INFN sites are registered, without considering their status (T1, T2, or T3 sites). An interesting use case were able to cover via the federation are disk-less Tier3s. The caching solution allows to operate a local storage with minimal human intervention: transfers are automatically done on a single file basis, and the cache is maintained operational by automatic removal of old files.

  13. The Federal Air Pollution Program.

    ERIC Educational Resources Information Center

    National Air Pollution Control Administration (DHEW), Washington, DC.

    Described is the Federal air pollution program as it was in 1967. The booklet is divided into these major topics: History of the Federal Program; Research; Assistance to State and Local Governments; Abatement and Prevention of Air Pollution; Control of Motor Vehicle Pollution; Information and Education; and Conclusion. Federal legislation has…

  14. The Federal Role in Education

    ERIC Educational Resources Information Center

    Hill, Paul T.

    2000-01-01

    In this paper, the author discusses the federal role in education, which raises fundamental questions about how federal programs affect the schools. He suggests principles for a new federal role and shows how government policies have made schools more formal and complex; engineered political pressures that distorted schools' operations and…

  15. Science in the Federal Government.

    ERIC Educational Resources Information Center

    Thibodeau, Sharon Gibbs

    1985-01-01

    Examines the realm of science and the federal government made evident in the 1950s by A. Hunter Dupree's classic work on the subject. Federal science before 1940, federal science since 1940, and sources of historical materials are among the major areas considered. (JN)

  16. Inhibition of eIF2α dephosphorylation inhibits ErbB2-induced deregulation of mammary acinar morphogenesis

    PubMed Central

    Sequeira, Sharon J; Wen, Huei Chi; Avivar-Valderas, Alvaro; Farias, Eduardo F; Aguirre-Ghiso, Julio A

    2009-01-01

    Background The ErbB2/Her2/Neu receptor tyrosine kinase is amplified in ~30% of human breast cancers. Phosphorylation of the translation initiation factor, eIF2α inhibits global protein synthesis and activates a stress signaling and growth suppressive program. We have shown that forced phosphorylation of eIF2α can suppress head and neck, colorectal carcinoma and multiple myeloma tumor growth and/or survival. Here we explore whether ErbB2 modulates eIF2α phosphorylation and whether forced phosphorylation of the latter can antagonize ErbB2 deregulation of mammary acinar morphogenesis. Results We tested whether ErbB2 signaling influenced eIF2α signaling and whether enhanced phosphorylation of the latter affected ErbB2-deregulated mammary acinar development. We obtained stable MCF10A cells overexpressing wild-type (Wt) Neu/ErbB2 or a constitutively active (CA) variant via retroviral delivery or mammary tumor cells from MMTV-Neu tumors. Western blotting, RT-PCR and confocal microscopy were used to analyze the effects of ErbB2 activation on eIF2α signaling and the effect of the GADD34-PP1C inhibitor salubrinal. Wt- and MMTV-Neu cells formed aberrant acini structures resembling DCIS, while CA-ErbB2 overexpression induced invasive lesions. In these structures we found that CA-ErbB2 but not the Wt variant significantly down-regulated the pro-apoptotic gene CHOP. This occurred without apparent modulation of basal phosphorylation of PERK and eIF2α or induction of its downstream target ATF4. However, inhibition of eIF2α dephosphorylation with salubrinal was sufficient to inhibit Wt- and CA-ErbB2- as well as MMTV-Neu-induced deregulation of acinar growth. This was linked to enhanced CHOP expression, inhibition of proliferation, induction of apoptosis and luminal clearing in Wt-ErbB2 and to inhibition of cyclin D1 levels and subsequent proliferation in CA-ErbB2 cells. Conclusion Depending on the strength of ErbB2 signaling there is a differential regulation of CHOP and e

  17. Federal Republic of Germany.

    PubMed

    1987-05-01

    The population of the Federal Republic of Germany (FRG) was an estimated 61 million (including West Berlin) in 1986 and is in the process of declining gradually as a result of low birth rates. The infant mortality rate is 11/1000, while life expectancy is 73.4 years for women and 67.2 years for men. Of the work force of 27.6 million, 5.4% are engaged in agriculture, 41.6% work in industry and commerce, 10% are employed by the government, and 42.7% are in the service sector. The gross national product was US$898.8 billion in 1986, with an annual growth rate of 2.6% and a per capita income of $10,680. The government is parliamentary and based on a democratic constitution emphasizing protection of individual liberty and divided power in a federal structure. Political life since the establishment of the FRG in 1949 has been characterized by remarkable stability and orderly succession. The FRG ranks among the most important economic powers in the world. The economy is largely export oriented, with 25-30% of the gross national product shipped abroad each year. Competition and free enterprise are fostered, but the state participates in the ownership and management of major sections of the economy, including public services. A major concern at present is the country's ability to adapt to new markets and to develop sophisticated technologies.

  18. Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood pressure, adiposity, cholesterol metabolism and social interaction in mouse offspring.

    PubMed

    Lee, Kuan-I; Chiang, Chin-Wei; Lin, Hui-Ching; Zhao, Jin-Feng; Li, Cheng-Ta; Shyue, Song-Kun; Lee, Tzong-Shyuan

    2016-05-01

    Long-term exposure to di-(2-ethylhexyl) phthalate (DEHP) is highly associated with carcinogenicity, fetotoxicity, psychological disorders and metabolic diseases, but the detrimental effects and mechanisms are not fully understood. We investigated the effect of exposing mouse mothers to DEHP, and the underlying mechanism, on blood pressure, obesity and cholesterol metabolism as well as psychological and learning behaviors in offspring. Tail-cuff plethysmography was used for blood pressure measurement; Western blot used was for phosphorylation and expression of protein; hematoxylin and eosin staining, Nissl staining and Golgi staining were used for histological examination. The serum levels of cholesterol, triglycerides and glucose were measured by blood biochemical analysis. Hepatic cholesterol and triglyceride levels were assessed by colorimetric assay kits. Offspring behaviors were evaluated by open-field activity, elevated plus maze, social preference test and Morris water maze. Maternal DEHP exposure deregulated the phosphorylation of endothelial nitric oxide synthase and upregulated angiotensin type 1 receptor in offspring, which led to increased blood pressure. It led to obesity in offspring by increasing the size of adipocytes in white adipose tissue and number of adipocytes in brown adipose tissue. It increased the serum level of cholesterol in offspring by decreasing the hepatic capacity for cholesterol clearance. The impaired social interaction ability induced by maternal DEHP exposure might be due to abnormal neuronal development. Collectively, our findings provide new evidence that maternal exposure to DEHP has a lasting effect on the physiological functions of the vascular system, adipose tissue and nerve system in offspring.

  19. Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure.

    PubMed

    Salker, Madhuri S; Christian, Mark; Steel, Jennifer H; Nautiyal, Jaya; Lavery, Stuart; Trew, Geoffrey; Webster, Zoe; Al-Sabbagh, Marwa; Puchchakayala, Goverdhan; Föller, Michael; Landles, Christian; Sharkey, Andrew M; Quenby, Siobhan; Aplin, John D; Regan, Lesley; Lang, Florian; Brosens, Jan J

    2011-10-16

    Infertility and recurrent pregnancy loss (RPL) are prevalent but distinct causes of reproductive failure that often remain unexplained despite extensive investigations. Analysis of midsecretory endometrial samples revealed that SGK1, a kinase involved in epithelial ion transport and cell survival, is upregulated in unexplained infertility, most prominently in the luminal epithelium, but downregulated in the endometrium of women suffering from RPL. To determine the functional importance of these observations, we first expressed a constitutively active SGK1 mutant in the luminal epithelium of the mouse uterus. This prevented expression of certain endometrial receptivity genes, perturbed uterine fluid handling and abolished embryo implantation. By contrast, implantation was unhindered in Sgk1-/- mice, but pregnancy was often complicated by bleeding at the decidual-placental interface and fetal growth retardation and subsequent demise. Compared to wild-type mice, Sgk1-/- mice had gross impairment of pregnancy-dependent induction of genes involved in oxidative stress defenses. Relative SGK1 deficiency was also a hallmark of decidualizing stromal cells from human subjects with RPL and sensitized these cells to oxidative cell death. Thus, depending on the cellular compartment, deregulated SGK1 activity in cycling endometrium interferes with embryo implantation, leading to infertility, or predisposes to pregnancy complications by rendering the feto-maternal interface vulnerable to oxidative damage.

  20. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia

    PubMed Central

    Irvine, David A.; Zhang, Bin; Kinstrie, Ross; Tarafdar, Anuradha; Morrison, Heather; Campbell, Victoria L.; Moka, Hothri A.; Ho, Yinwei; Nixon, Colin; Manley, Paul W.; Wheadon, Helen; Goodlad, John R.; Holyoake, Tessa L.; Bhatia, Ravi; Copland, Mhairi

    2016-01-01

    Targeting the Hedgehog (Hh) pathway represents a potential leukaemia stem cell (LSC)-directed therapy which may compliment tyrosine kinase inhibitors (TKIs) to eradicate LSC in chronic phase (CP) chronic myeloid leukaemia (CML). We set out to elucidate the role of Hh signaling in CP-CML and determine if inhibition of Hh signaling, through inhibition of smoothened (SMO), was an effective strategy to target CP-CML LSC. Assessment of Hh pathway gene and protein expression demonstrated that the Hh pathway is activated in CD34+ CP-CML stem/progenitor cells. LDE225 (Sonidegib), a small molecule, clinically investigated SMO inhibitor, used alone and in combination with nilotinib, inhibited the Hh pathway in CD34+ CP-CML cells, reducing the number and self-renewal capacity of CML LSC in vitro. The combination had no effect on normal haemopoietic stem cells. When combined, LDE225 + nilotinib reduced CD34+ CP-CML cell engraftment in NSG mice and, upon administration to EGFP+ /SCLtTA/TRE-BCR-ABL mice, the combination enhanced survival with reduced leukaemia development in secondary transplant recipients. In conclusion, the Hh pathway is deregulated in CML stem and progenitor cells. We identify Hh pathway inhibition, in combination with nilotinib, as a potentially effective therapeutic strategy to improve responses in CP-CML by targeting both stem and progenitor cells. PMID:27157927

  1. Biofluid metabotyping of occupationally exposed subjects to air pollution demonstrates high oxidative stress and deregulated amino acid metabolism

    PubMed Central

    Pradhan, Surya Narayan; Das, Aleena; Meena, Ramovatar; Nanda, Ranjan Kumar; Rajamani, Paulraj

    2016-01-01

    Occupational exposure to air pollution induces oxidative stress and prolonged exposure increases susceptibility to cardiovascular and respiratory diseases in several working groups. Biofluid of these subjects may reflect perturbed metabolic phenotypes. In this study we carried out a comparative molecular profiling study using parallel biofluids collected from subjects (n = 85) belonging to auto rickshaw drivers (ARD), traffic cops (TC) and office workers (OW). Higher levels of oxidative stress and inflammation markers in serum of ARD subjects were observed as compared to OW and TC. Uni and multivariate analyses of metabolites identified in urine by 1H NMR revealed 11 deregulated molecules in ARD subjects and involved in phenylalanine, histidine, arginine and proline metabolism. Despite contribution of confounding factors like exposure period, dietary factors including smoking and alcohol status, our results demonstrate existence of exposure specific metabotypes in biofluids of ARD, OW and TC groups. Monitoring serum oxidative stress and inflammation markers and urine metabolites by NMR may be useful to characterize perturbed metabolic phenotypes in populations exposed to urban traffic air pollution. PMID:27767182

  2. New Methodology for Evaluating Optimal Pricing for Primary Regulation of Deregulated Power Systems under Steady State Condition

    NASA Astrophysics Data System (ADS)

    Satyaramesh, P. V.; RadhaKrishna, C.

    2013-06-01

    A generalized pricing structure for procurement of power under frequency ancillary service is developed in this paper. It is a frequency linked-price model and suitable for deregulation market environment. This model takes into consideration: governor characteristics and frequency characteristics of generator as additional parameters in load flow method. The main objective of the new approach proposed in this paper is to establish bidding price structure for frequency regulation services in competitive ancillary electrical markets under steady state condition. Lot of literatures are available for calculating the frequency deviations with respect to load changes by using dynamic simulation methods. But in this paper, the model computes the frequency deviations for additional requirements of power under steady state with considering power system network topology. An attempt is also made in this paper to develop optimal bidding price structure for the frequency-regulated systems. It gives a signal to traders or bidders that the power demand can be assessed more accurately much closer to real time and helps participants bid more accurate quantities on day-ahead market. The recent trends of frequency linked-price model existing in Indian power systems issues required for attention are also dealt in this paper. Test calculations have been performed on 30-bus system. The paper also explains adoptability of 33 this model to practical Indian power system. The results presented are analyzed and useful conclusions are drawn.

  3. Expression of a deregulated tobacco nitrate reductase gene in potato increases biomass production and decreases nitrate concentration in all organs.

    PubMed

    Djennane, Samia; Quilleré, Isabelle; Leydecker, Marie-Thérèse; Meyer, Christian; Chauvin, Jean-Eric

    2004-09-01

    We investigated the physiological consequences for nitrogen metabolism and growth of the deregulated expression of an N-terminal-deleted tobacco nitrate reductase in two lines of potato (Solanum tuberosum L. cv Safrane). The transgenic plants showed a higher biomass accumulation, especially in tubers, but a constant nitrogen content per plant. This implies that the transformed lines had a reduced nitrogen concentration per unit of dry weight. A severe reduction in nitrate concentrations was also observed in all organs, but was more apparent in tubers where nitrate was almost undetectable in the transgenic lines. In leaves and roots, but not tubers, this nitrate decrease was accompanied by a statistically significant increase in the level of malate, which acts as a counter-anion for nitrate reduction. Apart from glutamine in tubers, no major changes in amino acid concentration were seen in leaves, roots or tubers. We conclude that enhancement of nitrate reduction rate leads to higher biomass production, probably by allowing a better allocation of N-resources to photosynthesis and C-metabolism.

  4. Importance of maternal diabetes on the chronological deregulation of the intrauterine development: an experimental study in rat.

    PubMed

    Salazar García, Marcela; Reyes Maldonado, Elba; Revilla Monsalve, María Cristina; Villavicencio Guzmán, Laura; Reyes López, Alfonso; Sánchez-Gómez, Concepción

    2015-01-01

    We investigated whether maternal diabetes induced in rats using streptozotocin (STZ) on Day 5 of pregnancy affects the intrauterine developmental timeline. A total of 30 pregnant Sprague-Dawley diabetic rats (DRs) and 20 control rats (CRs) were used to obtain 21-day fetuses (F21) and newborn (NB) pups. Gestational age, weight, and body size were recorded as were the maxillofacial morphometry and morphohistological characteristics of the limbs. In DRs, pregnancy continued for ∼1.7 days, and delivery occurred 23 days postcoitus (DPC). In this group, the number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group had lower weights and were smaller; moreover, the morphological characteristics of the maxillofacial structures, derived from the neural crest, were discordant with their chronological gestational age, resembling 18- to 19-day-old fetuses. These deficiencies were counterbalanced in NB pups. We conclude that hyperglycemia, which results from maternal diabetes and precedes embryo implantation, deregulates the intrauterine developmental timeline, restricts embryo-fetal growth, and primarily delays the remodeling and maturation of the structures derived from neural crest cells.

  5. ERG transcriptional networks in primary acute leukemia cells implicate a role for ERG in deregulated kinase signaling.

    PubMed

    Bock, Juliane; Mochmann, Liliana H; Schlee, Cornelia; Farhadi-Sartangi, Nasrin; Göllner, Stefanie; Müller-Tidow, Carsten; Baldus, Claudia D

    2013-01-01

    High expression of the E26 transforming sequence related gene (ERG) is associated with poor prognosis in a subgroup of leukemia patients with acute myeloid (AML) and acute T-lymphoblastic leukemia (T-ALL). In a previous study we proposed that ERG overexpression may deregulate several signaling cascades in acute leukemia. Herein, we further expand those studies by identifying a consensus of biological targets in primary blasts of newly diagnosed acute leukemia patients. Our findings of chromatin immunoprecipitation-on-chip of primary samples revealed 48 significantly enriched single genes including DAAM1 and NUMB. Significantly enriched signaling pathways included WNT/β-catenin, p53, and PI3K/AKT with ERG overexpression inducing dephosphorylation of AKT(Ser473) relative to non ERG expressing K562 cells. Cell based ERG overexpression studies also revealed drug resistance to multi-kinase inhibitor, BAY 43-9006 (Sorafenib) and to the tyrosine kinase inhibitor TKI258. Thus in primary leukemic cells, ERG may contribute to the dysregulation of kinase signaling, which results in resistance to kinase inhibitors.

  6. IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation.

    PubMed

    Oktay, Yavuz; Ülgen, Ege; Can, Özge; Akyerli, Cemaliye B; Yüksel, Şirin; Erdemgil, Yiğit; Durası, I Melis; Henegariu, Octavian Ioan; Nanni, E Paolo; Selevsek, Nathalie; Grossmann, Jonas; Erson-Omay, E Zeynep; Bai, Hanwen; Gupta, Manu; Lee, William; Turcan, Şevin; Özpınar, Aysel; Huse, Jason T; Sav, M Aydın; Flanagan, Adrienne; Günel, Murat; Sezerman, O Uğur; Yakıcıer, M Cengiz; Pamir, M Necmettin; Özduman, Koray

    2016-06-10

    The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17-16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94-27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association.

  7. Biofluid metabotyping of occupationally exposed subjects to air pollution demonstrates high oxidative stress and deregulated amino acid metabolism

    NASA Astrophysics Data System (ADS)

    Pradhan, Surya Narayan; Das, Aleena; Meena, Ramovatar; Nanda, Ranjan Kumar; Rajamani, Paulraj

    2016-10-01

    Occupational exposure to air pollution induces oxidative stress and prolonged exposure increases susceptibility to cardiovascular and respiratory diseases in several working groups. Biofluid of these subjects may reflect perturbed metabolic phenotypes. In this study we carried out a comparative molecular profiling study using parallel biofluids collected from subjects (n = 85) belonging to auto rickshaw drivers (ARD), traffic cops (TC) and office workers (OW). Higher levels of oxidative stress and inflammation markers in serum of ARD subjects were observed as compared to OW and TC. Uni and multivariate analyses of metabolites identified in urine by 1H NMR revealed 11 deregulated molecules in ARD subjects and involved in phenylalanine, histidine, arginine and proline metabolism. Despite contribution of confounding factors like exposure period, dietary factors including smoking and alcohol status, our results demonstrate existence of exposure specific metabotypes in biofluids of ARD, OW and TC groups. Monitoring serum oxidative stress and inflammation markers and urine metabolites by NMR may be useful to characterize perturbed metabolic phenotypes in populations exposed to urban traffic air pollution.

  8. Phosphoprotein network analysis of white adipose tissues unveils deregulated pathways in response to high-fat diet

    PubMed Central

    Asfa, Alli Shaik; Qiu, Beiying; Wee, Sheena; Choi, Hyungwon; Gunaratne, Jayantha; Tergaonkar, Vinay

    2016-01-01

    Despite efforts in the last decade, signaling aberrations associated with obesity remain poorly understood. To dissect molecular mechanisms that define this complex metabolic disorder, we carried out global phosphoproteomic analysis of white adipose tissue (WAT) from mice fed on low-fat diet (LFD) and high-fat diet (HFD). We quantified phosphorylation levels on 7696 peptides, and found significant differential phosphorylation levels in 282 phosphosites from 191 proteins, including various insulin-responsive proteins and metabolic enzymes involved in lipid homeostasis in response to high-fat feeding. Kinase-substrate prediction and integrated network analysis of the altered phosphoproteins revealed underlying signaling modulations during HFD-induced obesity, and suggested deregulation of lipogenic and lipolytic pathways. Mutation of the differentially-regulated novel phosphosite on cytoplasmic acetyl-coA forming enzyme ACSS2 (S263A) upon HFD-induced obesity led to accumulation of serum triglycerides and reduced insulin-responsive AKT phosphorylation as compared to wild type ACSS2, thus highlighting its role in obesity. Altogether, our study presents a comprehensive map of adipose tissue phosphoproteome in obesity and reveals many previously unknown candidate phosphorylation sites for future functional investigation. PMID:27180971

  9. WNT10B functional dualism: beta-catenin/Tcf-dependent growth promotion or independent suppression with deregulated expression in cancer.

    PubMed

    Yoshikawa, Hirohide; Matsubara, Kenichi; Zhou, Xiaoling; Okamura, Shu; Kubo, Takahiko; Murase, Yaeko; Shikauchi, Yuko; Esteller, Manel; Herman, James G; Wei Wang, Xin; Harris, Curtis C

    2007-11-01

    We found aberrant DNA methylation of the WNT10B promoter region in 46% of primary hepatocellular carcinoma (HCC) and 15% of colon cancer samples. Three of 10 HCC and one of two colon cancer cell lines demonstrated low or no expression, and 5-aza-2'deoxycytidine reactivated WNT10B expression with the induction of demethylation, indicating that WNT10B is silenced by DNA methylation in some cancers, whereas WNT10B expression is up-regulated in seven of the 10 HCC cell lines and a colon cancer cell line. These results indicate that WNT10B can be deregulated by either overexpression or silencing in cancer. We found that WNT10B up-regulated beta-catenin/Tcf activity. However, WNT10B-overexpressing cells demonstrated a reduced growth rate and anchorage-independent growth that is independent of the beta-catenin/Tcf activation, because mutant beta-catenin-transduced cells did not suppress growth, and dominant-negative hTcf-4 failed to alleviate the growth suppression by WNT10B. Although WNT10B expression alone inhibits cell growth, it acts synergistically with the fibroblast growth factor (FGF) to stimulate cell growth. WNT10B is bifunctional, one function of which is involved in beta-catenin/Tcf activation, and the other function is related to the down-regulation of cell growth through a different mechanism. We suggest that FGF switches WNT10B from a negative to a positive cell growth regulator.

  10. Importance of Maternal Diabetes on the Chronological Deregulation of the Intrauterine Development: An Experimental Study in Rat

    PubMed Central

    Salazar García, Marcela; Reyes Maldonado, Elba; Revilla Monsalve, María Cristina; Villavicencio Guzmán, Laura; Reyes López, Alfonso; Sánchez-Gómez, Concepción

    2015-01-01

    We investigated whether maternal diabetes induced in rats using streptozotocin (STZ) on Day 5 of pregnancy affects the intrauterine developmental timeline. A total of 30 pregnant Sprague-Dawley diabetic rats (DRs) and 20 control rats (CRs) were used to obtain 21-day fetuses (F21) and newborn (NB) pups. Gestational age, weight, and body size were recorded as were the maxillofacial morphometry and morphohistological characteristics of the limbs. In DRs, pregnancy continued for ∼1.7 days, and delivery occurred 23 days postcoitus (DPC). In this group, the number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group had lower weights and were smaller; moreover, the morphological characteristics of the maxillofacial structures, derived from the neural crest, were discordant with their chronological gestational age, resembling 18- to 19-day-old fetuses. These deficiencies were counterbalanced in NB pups. We conclude that hyperglycemia, which results from maternal diabetes and precedes embryo implantation, deregulates the intrauterine developmental timeline, restricts embryo-fetal growth, and primarily delays the remodeling and maturation of the structures derived from neural crest cells. PMID:25756053

  11. Biofluid metabotyping of occupationally exposed subjects to air pollution demonstrates high oxidative stress and deregulated amino acid metabolism.

    PubMed

    Pradhan, Surya Narayan; Das, Aleena; Meena, Ramovatar; Nanda, Ranjan Kumar; Rajamani, Paulraj

    2016-10-21

    Occupational exposure to air pollution induces oxidative stress and prolonged exposure increases susceptibility to cardiovascular and respiratory diseases in several working groups. Biofluid of these subjects may reflect perturbed metabolic phenotypes. In this study we carried out a comparative molecular profiling study using parallel biofluids collected from subjects (n = 85) belonging to auto rickshaw drivers (ARD), traffic cops (TC) and office workers (OW). Higher levels of oxidative stress and inflammation markers in serum of ARD subjects were observed as compared to OW and TC. Uni and multivariate analyses of metabolites identified in urine by (1)H NMR revealed 11 deregulated molecules in ARD subjects and involved in phenylalanine, histidine, arginine and proline metabolism. Despite contribution of confounding factors like exposure period, dietary factors including smoking and alcohol status, our results demonstrate existence of exposure specific metabotypes in biofluids of ARD, OW and TC groups. Monitoring serum oxidative stress and inflammation markers and urine metabolites by NMR may be useful to characterize perturbed metabolic phenotypes in populations exposed to urban traffic air pollution.

  12. Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor κB–mediated pathogenic pathways

    PubMed Central

    Swarup, Vivek; Phaneuf, Daniel; Dupré, Nicolas; Petri, Susanne; Strong, Michael; Kriz, Jasna

    2011-01-01

    TDP-43 (TAR DNA-binding protein 43) inclusions are a hallmark of amyotrophic lateral sclerosis (ALS). In this study, we report that TDP-43 and nuclear factor κB (NF-κB) p65 messenger RNA and protein expression is higher in spinal cords in ALS patients than healthy individuals. TDP-43 interacts with and colocalizes with p65 in glial and neuronal cells from ALS patients and mice expressing wild-type and mutant TDP-43 transgenes but not in cells from healthy individuals or nontransgenic mice. TDP-43 acted as a co-activator of p65, and glial cells expressing higher amounts of TDP-43 produced more proinflammatory cytokines and neurotoxic mediators after stimulation with lipopolysaccharide or reactive oxygen species. TDP-43 overexpression in neurons also increased their vulnerability to toxic mediators. Treatment of TDP-43 mice with Withaferin A, an inhibitor of NF-κB activity, reduced denervation in the neuromuscular junction and ALS disease symptoms. We propose that TDP-43 deregulation contributes to ALS pathogenesis in part by enhancing NF-κB activation and that NF-κB may constitute a therapeutic target for the disease. PMID:22084410

  13. 75 FR 38999 - Federal Perkins Loan Program: Federal Family Education Loan Program and William D. Ford Federal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-07

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF EDUCATION Federal Perkins Loan Program: Federal Family Education Loan Program and William D. Ford Federal Direct Loan Program AGENCY: Office of Postsecondary Education, Department of Education. ACTION:...

  14. 78 FR 60700 - Source Specific Federal Implementation Plan for Implementing Best Available Retrofit Technology...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ..., due to new uncertainties related to the potential deregulation of the retail electricity market in... filed a Form 8-K with the United States Securities and Exchange Commission disclosing the uncertainty... uncertainty regarding the ACC's consideration of deregulation and the potential for a deregulated...

  15. 41 CFR 102-79.40 - Can Federal agencies allot space in Federal buildings to Federal credit unions?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false Can Federal agencies... Credit Unions § 102-79.40 Can Federal agencies allot space in Federal buildings to Federal credit unions? Yes, in accordance with 12 U.S.C. 1770, Federal agencies may allot space in Federal buildings...

  16. 41 CFR 102-79.40 - Can Federal agencies allot space in Federal buildings to Federal credit unions?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false Can Federal agencies... Credit Unions § 102-79.40 Can Federal agencies allot space in Federal buildings to Federal credit unions? Yes, in accordance with 12 U.S.C. 1770, Federal agencies may allot space in Federal buildings...

  17. 75 FR 18014 - Federal Highway Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-08

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Highway Administration AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of...: Federal Highway Administration, Kentucky Division: Mr. Greg Rawlings, Transportation Specialist, 330...

  18. 78 FR 9771 - Federal Highway Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-11

    ... Federal Highway Administration Notice of Final Federal Agency Action on Proposed Transportation Project in Illinois and Indiana AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of limitation on..., Federal Highway Administration, 3250 Executive Park Drive, Springfield, Illinois 62703, Phone: (217)...

  19. 78 FR 41183 - Federal Aviation Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Meeting: RTCA Program Management Committee AGENCY: Federal Aviation.... Paige Williams, Management Analyst, NextGen, Business Operations Group, Federal Aviation...

  20. Deregulated Expression of the Human Tumor Marker CEA and CEA Family Member CEACAM6 Disrupts Tissue Architecture and Blocks Colonocyte Differentiation1

    PubMed Central

    Ilantzis, Christian; Demarte, Luisa; Screaton, Robert A; Stanners, Clifford P

    2002-01-01

    Abstract Human carcinoembryonic antigen (CEA) and the CEA family member CEACAM6 (formerly nonspecific cross-reacting antigen [NCA]) function in vitro, at least, as homotypic intercellular adhesion molecules and, in model systems, can block the terminal differentiation and anoikis of several different cell types. We have recently demonstrated that the increased cell surface levels of CEA and CEACAM6 in purified human colonocytes from freshly excised, well to poorly differentiated colon carcinomas are inversely correlated with the degree of cellular differentiation. Thus, deregulated expression of CEA/CEACAM6 could directly contribute to colon tumorigenesis by the inhibition of terminal differentiation and anoikis. Evidence against this view includes the common observation of increased CEA/CEACAM6 expression as normal colonocytes differentiate in their migration up colonic crypt walls. We report here the direct effects of deregulated overexpression of CEA/CEACAM6, at levels observed in colorectal carcinomas, on the differentiation of two human colonic cell lines, SW-1222 and Caco-2. Stable transfectants of both of these cell lines that constitutively express 10- to 30-fold higher cell surface levels of CEA/CEACAM6 than endogenous levels failed to polarize and differentiate into glandular structures in monolayer or 3D culture or to form colonic crypts in a tissue architecture assay in nude mice. In addition, these transfectants were found to exhibit increased tumorigenicity in nude mice. These results thus support the contention that deregulated overexpression of CEA and CEACAM6 could provide a tumorigenic contribution to colon carcinogenesis. PMID:11896570

  1. Deregulation Impact in Negotiating a New Electrical Contract Between NASA Glenn Research Center at Lewis Field and FirstEnergy Corp., Cleveland, Ohio, USA

    NASA Technical Reports Server (NTRS)

    Quach, Quyen T.; Zala, Laszlo F.

    2002-01-01

    The governor of the State of Ohio signed amended substitute Senate bill 3 on July 6, 1999, requiring Ohio's electric industry to change from a monopoly environment to a competitive electric environment for generation services. The start date for competitive retail generation services was set for January 1, 2001. This new deregulation law allowed all Ohioans to choose the supplier of generation service, but the transmission and distribution would remain regulated. It also required electric utilities to unbundle the three main components (generation, transmission, and distribution) and make other changes designed to produce a competitive electric generation market. While deregulation was taking shape, the NASA Glenn Research Center electrical contract with FirstEnergy Corp. of Cleveland, Ohio, was to expire on September 7, 1999. Glenn strategically evaluated and incorporated the impacts of electric deregulation in the negotiations. Glenn and FirstEnergy spent over a year in negotiations until the Glenn utility team and the FirstEnergy negotiating team came to an agreement in the fall of 2000, and a new contract became effective on January 1, 2001.

  2. The impossible dream? How Nuclear Electric, Ltd. pulled itself out of the ashes of government ownership and became highly competitive in a privatized and deregulating British power market

    SciTech Connect

    Maycock, P.

    1998-12-31

    The day was dark for Nuclear Electric plc. when the British government decided it would privatize and deregulate the electric utility industry. For years, Nuclear Electric and other UK-based fossil power producers had been operating in a regulated market where the state set and guaranteed the price of electricity. All that was changing in Britain as the government introduced competition and as customers looked forward to purchasing power from the lowest bidder. Essentially the situation in England was much the same as it is now in the US: there was major momentum toward deregulation. The reality of competition in Britain came as good news to many power producers--in particular those who kept the lights on cost effectively. Others, However, weren`t so optimistic, especially nuclear plants that traditionally bear higher safety and maintenance costs than their fossil counterparts. Taking its cues from the City (Britain`s Wall Street), the British government simply considered nuclear generators to be unreliable, high cost, unprofitable organizations incapable of surviving in a privatized environment. It therefore left its nuclear power plants off the docket when selling (privatizing) its generating capacity. This paper describes how Nuclear Electric Ltd. became competitive in a deregulated environment.

  3. HBx-dependent cell cycle deregulation involves interaction with cyclin E/A-cdk2 complex and destabilization of p27Kip1.

    PubMed

    Mukherji, Atish; Janbandhu, Vaibhao C; Kumar, Vijay

    2007-01-01

    The HBx (X protein of hepatitis B virus) is a promiscuous transactivator implicated to play a key role in hepatocellular carcinoma. However, HBx-regulated molecular events leading to deregulation of cell cycle or establishment of a permissive environment for hepatocarcinogenesis are not fully understood. Our cell culture-based studies suggested that HBx had a profound effect on cell cycle progression even in the absence of serum. HBx presence led to an early and sustained level of cyclin-cdk2 complex during the cell cycle combined with increased protein kinase activity of cdk2 heralding an early proliferative signal. The increased cdk2 activity also led to an early proteasomal degradation of p27(Kip1) that could be reversed by HBx-specific RNA interference and blocked by a chemical inhibitor of cdk2 or the T187A mutant of p27. Further, our co-immunoprecipitation and in vitro binding studies with recombinant proteins suggested a direct interaction between HBx and the cyclin E/A-cdk2 complex. Interference with different signalling cascades known to be activated by HBx suggested a constitutive requirement of Src kinases for the association of HBx with these complexes. Notably, the HBx mutant that did not interact with cyclin E/A failed to destabilize p27(Kip1) or deregulate the cell cycle. Thus HBx appears to deregulate the cell cycle by interacting with the key cell cycle regulators independent of its well-established role in transactivation.

  4. Federal Buildings Supplemental Survey 1993

    SciTech Connect

    1995-11-01

    The Energy Information Administration (EIA) of the US Department of Energy (DOE) is mandated by Congress to be the agency that collects, analyzes, and disseminates impartial, comprehensive data about energy including the volume consumed, its customers, and the purposes for which it is used. The Federal Buildings Supplemental Survey (FBSS) was conducted by EIA in conjunction with DOE`s Office of Federal Energy Management Programs (OFEMP) to gain a better understanding of how Federal buildings use energy. This report presents the data from 881 completed telephone interviews with Federal buildings in three Federal regions. These buildings were systematically selected using OFEMP`s specifications; therefore, these data do not statistically represent all Federal buildings in the country. The purpose of the FBSS was threefold: (1) to understand the characteristics of Federal buildings and their energy use; (2) to provide a baseline in these three Federal regions to measure future energy use in Federal buildings as required in EPACT; and (3) to compare building characteristics and energy use with the data collected in the CBECS.

  5. Federal Environmental Permitting Handbook

    SciTech Connect

    Not Available

    1991-05-01

    The handbook consists of eight chapters addressing permitting and licensing requirements under the Resource Conservation and Recovery Act (RCRA), the Comprehensive Environmental Response, Compensation, and Liability Act of 1980, as amended by the Superfund Amendments and Reauthorization Act of 1986 (CERCLA/SARA), the Atomic Energy Act (AEA), the Clean Air Act (CAA), the Clean Water Act (CWA), the Federal Insectide, Fungicide, and Rodenticide Act (FIFRA), the Safe Drinking Water Act (SDWA), and the Toxic Substances Control Act (TSCA). Each chapter consists of: (1) an introduction to the statute and permitting requirements; (2) a diagram illustrating the relationship between permitting requirements under the statute being discussed and permitting requirements from other environmental statutes which may have to be addressed when applying for a particular permit (e.g., when applying for a RCRA permit, permits and permit applications under the CWA, CAA, SDWA, etc. would have to be listed in the RCRA permit application); and, (3) a compilation of the permitting requirements for the regulatory program resulting from the statute. In addition, the Handbook contains a permitting keyword index and a listing of hotline telephone numbers for each of the statutes.

  6. Helping Federal Policymakers Understand and Support Data Literacy. Federal Spotlight

    ERIC Educational Resources Information Center

    Data Quality Campaign, 2014

    2014-01-01

    Current federal and state policies focus on improved results for students through quality teaching. Strategies in school improvement plans, data-driven teacher evaluation, assessments and rigorous standards, competency-based learning, and innovative digital platforms make teacher data use essential. While state and federal policies are asking…

  7. Federal Research: Peer Review Practices at Federal Science Agencies Vary.

    DTIC Science & Technology

    1999-03-01

    traditionally relied on independent reviews by peers. This report responds to your request that we study the peer review and other quality assurance processes...by peer review , (2) describe the federal government’s peer review policy, (3) describe the peer review practices of 12 federal agencies that conduct

  8. Emissions markets, power markets and market power: A study of the interactions between contemporary emissions markets and deregulated electricity markets

    NASA Astrophysics Data System (ADS)

    Dormady, Noah Christopher

    Chapter 1: A Monte Carlo Approach. The use of auctions to distribute tradeable property rights to firms in already heavily concentrated markets may further exacerbate the problems of market power that exist within those markets. This chapter provides a model of a two-stage emissions market modeled after a contemporary regional permit trading market in the United States, the Regional Greenhouse Gas Initiative, Inc. (RGGI). It then introduces Oligopsony 1.0, a C# software package constructed in the .NET environment that simulates uniform-price auctions using stochastic Monte Carlo simulation for modeling market power in tradeable property rights auctions. Monte Carlo methods add a probabilistic element to standard auction theoretic equilibria. The results of these simulations indicate that there can be significant non-linearities between profit and market power as exercised through strategic demand reduction. This analysis finds the optimum point of strategic demand reduction that enables the firm to exploit these non-linearities, and it determines the probability distributions of these optima using kernel density analysis. Chapter 2: An Experimental Approach. How will emerging auction-based emissions markets function within the context of today's deregulated auction-based electricity markets? This chapter provides an experimental analysis of a joint energy-emissions market. The impact of market power and collusion among dominant firms is evaluated to determine the extent to which an auction-based tradeable permit market influences performance in an adjacent electricity market. The experimental treatment design controls for a variety of real-world institutional features, including variable demand, permit banking, inter-temporal (multi-round) dynamics, a tightening cap, and resale. Results suggest that the exercise of market power significantly increases electricity auction clearing prices, without significantly increasing emissions

  9. Effect of neurotrophin-3 precursor on glutamate-induced calcium homeostasis deregulation in rat cerebellum granule cells.

    PubMed

    Safina, Dina R; Surin, Alexander M; Pinelis, Vsevolod G; Kostrov, Sergey V

    2015-12-01

    Neurotrophin-3 (NT-3) belongs to the family of highly conserved dimeric growth factors that controls the differentiation and activity of various neuronal populations. Mammals contain both the mature (NT-3) and the precursor (pro-NT-3) forms of neurotrophin. Members of the neurotrophin family are involved in the regulation of calcium homeostasis in neurons; however, the role of NT-3 and pro-NT-3 in this process remains unclear. The current study explores the effects of NT-3 and pro-NT-3 on disturbed calcium homeostasis and decline of mitochondrial potential induced by a neurotoxic concentration of glutamate (Glu; 100 µM) in the primary culture of rat cerebellar granule cells. In this Glu excitotoxicity model, mature NT-3 had no effect on the induced changes in Ca²⁺ homeostasis. In contrast, pro-NT-3 decreased the period of delayed calcium deregulation (DCD) and concurrent strong mitochondrial depolarization. According to the amplitude of the increase in the intracellular free Ca²⁺ concentration ([Ca²⁺]i ) and Fura-2 fluorescence quenching by Mn²⁺ within the first 20 sec of exposure to Glu, pro-NT-3 had no effect on the initial rate of Ca²⁺ entry into neurons. During the lag period preceding DCD, the mean amplitude of [Ca²⁺]i rise was 1.2-fold greater in the presence of pro-NT-3 than in the presence of Glu alone (1.67 ±  0.07 and 1.39 ± 0.04, respectively, P < 0.05). The Glu-induced changes in Са²⁺ homeostasis in the presence of pro-NT-3 likely are due to the decreased rate of Са²⁺ removal from the cytosol during the DCD latency period.

  10. Tyrosine kinase discoidin domain receptors DDR1 and DDR2 are coordinately deregulated in triple-negative breast cancer.

    PubMed

    Toy, Kathy A; Valiathan, Rajeshwari R; Núñez, Fernando; Kidwell, Kelley M; Gonzalez, Maria E; Fridman, Rafael; Kleer, Celina G

    2015-02-01

    Receptor kinases Discoidin Domain Receptors (DDRs) 1 and 2 are emerging as new therapeutic targets in breast cancer (BC). However, the expression of DDR proteins during BC progression and their association with BC subtypes remain poorly defined. Herein we report the first comprehensive immunohistochemical analyses of DDR protein expression in a wide range of breast tissues. DDR1 and DDR2 expression was investigated by immunohistochemistry in 218 samples of normal breast (n = 10), ductal carcinoma in situ (DCIS, n = 10), and invasive carcinomas (n = 198), arrayed in tissue microarrays with comprehensive clinical and follow-up information. Staining was evaluated for cell type, subcellular localization, percentage and intensity (scores 1-4), and association with disease subtype and outcome. In normal epithelium and DCIS, DDR1 was highly expressed, while DDR2 was negative in normal epithelium, and in DCIS it localized to cells at the epithelial-stromal interface. Of the 198 invasive carcinomas, DDR1 was high in 87 (44 %) and low in 103 (52 %), and DDR2 was high in 110 (56 %) and low in 87 (44 %). High DDR2 was associated with high tumor grade (P = 0.002), triple-negative subtype (TNBC) (P < 0.0001), and worse survival (P = 0.037). We discovered a novel concordant deregulation of DDR expression, with a DDR1(Low)/DDR2(High) profile significantly associated with TNBC, compared to luminal tumors (P = 0.012), and with worse overall survival. In conclusion, DDR2 upregulation occurs in DCIS, before stromal invasion, and may reflect epithelial-stromal cross-talk. A DDR1(Low)/DDR2(High) protein profile is associated with TNBC and may identify invasive carcinomas with worse prognosis.

  11. MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma.

    PubMed

    Sandoval, Juan; Díaz-Lagares, Angel; Salgado, Rocío; Servitje, Octavio; Climent, Fina; Ortiz-Romero, Pablo L; Pérez-Ferriols, Amparo; Garcia-Muret, Maria P; Estrach, Teresa; Garcia, Mar; Nonell, Lara; Esteller, Manel; Pujol, Ramon M; Espinet, Blanca; Gallardo, Fernando

    2015-04-01

    MicroRNAs usually regulate gene expression negatively, and aberrant expression has been involved in the development of several types of cancers. Microarray profiling of microRNA expression was performed to define a microRNA signature in a series of mycosis fungoides tumor stage (MFt, n=21) and CD30+ primary cutaneous anaplastic large cell lymphoma (CD30+ cALCL, n=11) samples in comparison with inflammatory dermatoses (ID, n=5). Supervised clustering confirmed a distinctive microRNA profile for cutaneous T-cell lymphoma (CTCL) with respect to ID. A 40 microRNA signature was found in MFt including upregulated onco-microRNAs (miR-146a, miR-142-3p/5p, miR-21, miR-181a/b, and miR-155) and downregulated tumor-suppressor microRNAs (miR-200ab/429 cluster, miR-10b, miR-193b, miR-141/200c, and miR-23b/27b). Regarding CD30+ cALCL, 39 differentially expressed microRNAs were identified. Particularly, overexpression of miR-155, miR-21, or miR-142-3p/5p and downregulation of the miR-141/200c clusters were observed. DNA methylation in microRNA gene promoters, as expression regulatory mechanism for deregulated microRNAs, was analyzed using Infinium 450K array and approximately one-third of the differentially expressed microRNAs showed significant DNA methylation differences. Two different microRNA methylation signatures for MFt and CD30+ cALCL were found. Correlation analysis showed an inverse relationship for microRNA promoter methylation and microRNA expression. These results reveal a subgroup-specific epigenetically regulated microRNA signatures for MFt and CD30+ cALCL patients.

  12. Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice

    PubMed Central

    Gil, Veronica S.; Howell, Louise; Zhang, Jiyuan; Kim, Chae H.; Stengel, Sven; Vega, Francisco; Zelent, Arthur

    2016-01-01

    ABSTRACT Histone deacetylase 9 (HDAC9) is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL). We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL). To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM) model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH) enhancer (Eμ). Here, we report that the Eμ-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD) with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of Eμ-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors. PMID:27799148

  13. IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation

    PubMed Central

    Oktay, Yavuz; Ülgen, Ege; Can, Özge; Akyerli, Cemaliye B.; Yüksel, Şirin; Erdemgil, Yiğit; Durası, İ. Melis; Henegariu, Octavian Ioan; Nanni, E. Paolo; Selevsek, Nathalie; Grossmann, Jonas; Erson-Omay, E. Zeynep; Bai, Hanwen; Gupta, Manu; Lee, William; Turcan, Şevin; Özpınar, Aysel; Huse, Jason T.; Sav, M. Aydın; Flanagan, Adrienne; Günel, Murat; Sezerman, O. Uğur; Yakıcıer, M. Cengiz; Pamir, M. Necmettin; Özduman, Koray

    2016-01-01

    The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17–16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94–27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association. PMID:27282637

  14. Distinct deregulation of the hypoxia inducible factor by PHD2 mutants identified in germline DNA of patients with polycythemia

    PubMed Central

    Ladroue, Charline; Hoogewijs, David; Gad, Sophie; Carcenac, Romain; Storti, Federica; Barrois, Michel; Gimenez-Roqueplo, Anne-Paule; Leporrier, Michel; Casadevall, Nicole; Hermine, Olivier; Kiladjian, Jean-Jacques; Baruchel, André; Fakhoury, Fadi; Bressac-de Paillerets, Brigitte; Feunteun, Jean; Mazure, Nathalie; Pouysségur, Jacques; Wenger, Roland H.; Richard, Stéphane; Gardie, Betty

    2012-01-01

    Background Congenital secondary erythrocytoses are due to deregulation of hypoxia inducible factor resulting in overproduction of erythropoietin. The most common germline mutation identified in the hypoxia signaling pathway is the Arginine 200-Tryptophan mutant of the von Hippel-Lindau tumor suppressor gene, resulting in Chuvash polycythemia. This mutant displays a weak deficiency in hypoxia inducible factor α regulation and does not promote tumorigenesis. Other von Hippel-Lindau mutants with more deleterious effects are responsible for von Hippel-Lindau disease, which is characterized by the development of multiple tumors. Recently, a few mutations in gene for the prolyl hydroxylase domain 2 protein (PHD2) have been reported in cases of congenital erythrocytosis not associated with tumor formation with the exception of one patient with a recurrent extra-adrenal paraganglioma. Design and Methods Five PHD2 variants, four of which were novel, were identified in patients with erythrocytosis. These PHD2 variants were functionally analyzed and compared with the PHD2 mutant previously identified in a patient with polycythemia and paraganglioma. The capacity of PHD2 to regulate the activity, stability and hydroxylation of hypoxia inducible factor α was assessed using hypoxia-inducible reporter gene, one-hybrid and in vitro hydroxylation assays, respectively. Results This functional comparative study showed that two categories of PHD2 mutants could be distinguished: one category with a weak deficiency in hypoxia inducible factor α regulation and a second one with a deleterious effect; the mutant implicated in tumor occurrence belongs to the second category. Conclusions As observed with germline von Hippel-Lindau mutations, there are functional differences between the PHD2 mutants with regards to hypoxia inducible factor regulation. PHD2 mutation carriers do, therefore, need careful medical follow-up, since some mutations must be considered as potential candidates for

  15. Carboxyl-terminal truncated HBx contributes to invasion and metastasis via deregulating metastasis suppressors in hepatocellular carcinoma

    PubMed Central

    Li, Weihua; Li, Man; Liao, Dongjiang; Lu, Xinpeng; Gu, Xia; Zhang, Qianqian; Zhang, Zhixiang; Li, Hui

    2016-01-01

    Hepatitis B virus (HBV) X protein (HBx), a trans-regulator, is frequently expressed in truncated form without carboxyl-terminus in hepatocellular carcinoma (HCC), but its functional mechanisms are not fully defined. In this report, we investigated frequency of this natural HBx mutant in HCCs and its functional significance. In 102 HBV-infected patients with HCC, C-terminal truncation of HBx, in contrast to full-length HBx, were more prevalent in tumors (70.6%) rather than adjacent non-tumorous tissues (29.4%) (p = 0.0032). Furthermore, two naturally-occurring HBx variants (HBxΔ31), which have 31 amino acids (aa) deleted (codons 123-125/124-126) at C-terminus were identified in tumors and found that the presence of HBxΔ31 significantly correlated with intrahepatic metastasis. We also show that over-expression of HBxΔ31 enhanced hepatoma cell invasion in vitro and metastasis in vivo compared to full-length HBx. Interestingly, HBxΔ31 exerts this function via down-regulating Maspin, RhoGDIα and CAPZB, a set of putative metastasis-suppressors in HCC, in part, by enhancing the binding of transcriptional repressor, myc-associated zinc finger protein (MAZ) to the promoters through physical association with MAZ. Notably, these HBxΔ31-repressed proteins were also significantly lower expression in a subset of HCC tissues with C-terminal HBx truncation than the adjacent non-tumorous tissues, highlighting the clinical significance of this novel HBxΔ31-driven metastatic molecular cascade. Our data suggest that C-terminal truncation of HBx, particularly breakpoints at 124aa, plays a role in enhancing hepatoma cell invasion and metastasis by deregulating a set of metastasis-suppressors partially through MAZ, thus uncovering a novel mechanism for the progression of HBV-associated hepatocarcinogenesis. PMID:27391153

  16. Nash equilibrium strategy in the deregulated power industry and comparing its lost welfare with Iran wholesale electricity market

    NASA Astrophysics Data System (ADS)

    Mousavi, Seyed Hosein; Nazemi, Ali; Hafezalkotob, Ashkan

    2016-07-01

    With the increasing use of different types of auctions in market designing, modeling of participants' behaviors to evaluate the market structure is one of the main discussions in the studies related to the deregulated power industries. In this article, we apply an approach of the optimal bidding behavior to the Iran wholesale electricity market as a restructured electric power industry and model how the participants of the market bid in the spot electricity market. The problem is formulated analytically using the Nash equilibrium concept composed of large numbers of players having discrete and very large strategy spaces. Then, we compute and draw supply curve of the competitive market in which all generators' proposed prices are equal to their marginal costs and supply curve of the real market in which the pricing mechanism is pay-as-bid. We finally calculate the lost welfare or inefficiency of the Nash equilibrium and the real market by comparing their supply curves with the competitive curve. We examine 3 cases on November 24 (2 cases) and July 24 (1 case), 2012. It is observed that in the Nash equilibrium on November 24 and demand of 23,487 MW, there are 212 allowed plants for the first case (plants are allowed to choose any quantity of generation except one of them that should be equal to maximum Power) and the economic efficiency or social welfare of Nash equilibrium is 2.77 times as much as the real market. In addition, there are 184 allowed plants for the second case (plants should offer their maximum power with different prices) and the efficiency or social welfare of Nash equilibrium is 3.6 times as much as the real market. On July 24 and demand of 42,421 MW, all 370 plants should generate maximum energy due to the high electricity demand that the economic efficiency or social welfare of the Nash equilibrium is about 2 times as much as the real market.

  17. Altered expression of the imprinted transcription factor PLAGL1 deregulates a network of genes in the human IUGR placenta

    PubMed Central

    Iglesias-Platas, Isabel; Martin-Trujillo, Alex; Petazzi, Paolo; Guillaumet-Adkins, Amy; Esteller, Manel; Monk, David

    2014-01-01

    Genomic imprinting is the epigenetic process that results in monoallelic expression of genes depending on parental origin. These genes are known to be critical for placental development and fetal growth in mammals. Aberrant epigenetic profiles at imprinted loci, such as DNA methylation defects, are surprisingly rare in pregnancies with compromised fetal growth, while variations in transcriptional output from the expressed alleles of imprinted genes are more commonly reported in pregnancies complicated with intrauterine growth restriction (IUGR). To determine if PLAGL1 and HYMAI, two imprinted transcripts deregulated in Transient Neonatal Diabetes Mellitus, are involved in non-syndromic IUGR we compared the expression and DNA methylation levels in a large cohort of placental biopsies from IUGR and uneventful pregnancies. This revealed that despite appropriate maternal methylation at the shared PLAGL1/HYMAI promoter, there was a loss of correlation between PLAGL1 and HYMAI expression in IUGR. This incongruity was due to higher HYMAI expression in IUGR gestations, coupled with PLAGL1 down-regulation in placentas from IUGR girls, but not boys. The PLAGL1 protein is a zinc-finger transcription factor that has been shown to be a master coordinator of a genetic growth network in mice. We observe PLAGL1 binding to the H19/IGF2 shared enhancers in placentae, with significant correlations between PLAGL1 levels with H19 and IGF2 expression levels. In addition, PLAGL1 binding and expression also correlate with expression levels of metabolic regulator genes SLC2A4, TCF4 and PPARγ1. Our results strongly suggest that fetal growth can be influenced by altered expression of the PLAGL1 gene network in human placenta. PMID:24993786

  18. The Federal Employees' Compensation Act.

    ERIC Educational Resources Information Center

    Nordlund, Willis J.

    1991-01-01

    The 1916 Federal Employees' Compensation Act is still the focal point around which the federal workers compensation program works today. The program has gone through many changes on its way to becoming a modern means of compensating workers for job-related injury, disease, and death. (Author)

  19. Sustainability in Brazilian Federal Universities

    ERIC Educational Resources Information Center

    Palma, Lisiane Celia; de Oliveira, Lessandra M.; Viacava, Keitiline R.

    2011-01-01

    Purpose: The purpose of this paper is to identify the number of courses related to sustainability offered in bachelor degree programs of business administration in Brazilian federal universities. Design/methodology/approach: An exploratory research was carried out based on a descriptive scope. The process of mapping federal universities in Brazil…

  20. Federal, State, and Local regulations

    SciTech Connect

    Kelly, J.M.; Brandenburg, B.L. )

    1991-08-01

    This article is a review of federal, state, and local regulations pertinent treatment of leachate from hazardous materials landfills in California. The topics covered include under federal regulations: pretreatment, whole-effluent toxicity, hazardous waste regulation; under state regulations: hazardous waste regulations, air toxics, environmental quality act; under local regulations: local limits, toxicity-regional water quality board, air emissions and district code.

  1. Federal Funding in the Delta.

    ERIC Educational Resources Information Center

    Reeder, Richard J.; Calhoun, Samuel D.

    2002-01-01

    The Lower Mississippi Delta region, especially the rural Delta, faces many economic challenges. The rural Delta has received much federal aid in basic income support and funding for human resource development, but less for community resource programs, which are important for economic development. Federal aid to the Delta is analyzed in terms of…

  2. When Federalism Works. Final Report.

    ERIC Educational Resources Information Center

    Peterson, Paul E.; And Others

    A study of the implementation of six major federal education policies in four urban school districts (Baltimore, Maryland; Milwaukee, Wisconsin; San Diego, California; and Dade County, Florida) generally supported a new theory of federalism. Research data were drawn from statistical reports and from interviews with over 150 persons at local,…

  3. Telecommuting in the Federal Workforce

    DTIC Science & Technology

    2001-12-01

    Act under the Truman Administration. The Hoover Administration recommended examining ways to improve the administrative services of the Federal...www.businessweek.com/1998/41/b3599150.htm 53. O’Hara, Colleen , and Haubold, Natasha, Federal Computer Week, “Telecommuting Hits a Roadblock,” March

  4. 75 FR 14057 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-40; Introduction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

    ... Federal Acquisition Regulation; Federal Acquisition Circular 2005-40: Introduction, Small Entity... Acquisition Regulation; Federal Acquisition Circular 2005-40; Introduction AGENCIES: Department of Defense...

  5. State/Federal Regulatory Considerations

    EPA Pesticide Factsheets

    This page contains presentations from the Brown to Green: Make the Connection to Renewable Energy workshop held in Santa Fe, New Mexico, during December 10-11, 2008, regarding State/Federal Regulatory Considerations.

  6. Federal Firefighter Pay Equity Act

    THOMAS, 111th Congress

    Rep. Connolly, Gerald E. [D-VA-11

    2009-07-13

    07/31/2009 Referred to the Subcommittee on Federal Workforce, Post Office, and the District of Columbia. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  7. Federal Firefighter Pay Equity Act

    THOMAS, 112th Congress

    Rep. Connolly, Gerald E. [D-VA-11

    2011-03-14

    04/01/2011 Referred to the Subcommittee on Federal Workforce, U.S. Postal Service, and Labor Policy. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  8. Federal Employees Responsible Investment Act

    THOMAS, 112th Congress

    Rep. Langevin, James R. [D-RI-2

    2011-06-03

    06/20/2011 Referred to the Subcommittee on Federal Workforce, U.S. Postal Service, and Labor Policy . (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  9. 2016 Federal Green Challenge Awards

    EPA Pesticide Factsheets

    We are pleased to recognize the following participants in the FGC for their significant efforts in improving the sustainability of their facilities and for their leadership in reducing the environmental footprint of federal government activities.

  10. Federal Life Insurance Transparency Act

    THOMAS, 112th Congress

    Rep. Connolly, Gerald E. [D-VA-11

    2011-01-05

    02/08/2011 Referred to the Subcommittee on Federal Workforce, U.S. Postal Service, and Labor Policy . (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  11. 1 CFR 12.1 - Federal Register.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 1 General Provisions 1 2014-01-01 2012-01-01 true Federal Register. 12.1 Section 12.1 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS OFFICIAL DISTRIBUTION WITHIN FEDERAL GOVERNMENT § 12.1 Federal Register. (a) Copies of the...

  12. 1 CFR 12.1 - Federal Register.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 1 General Provisions 1 2012-01-01 2012-01-01 false Federal Register. 12.1 Section 12.1 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS OFFICIAL DISTRIBUTION WITHIN FEDERAL GOVERNMENT § 12.1 Federal Register. (a) Copies of the...

  13. 1 CFR 12.1 - Federal Register.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 1 General Provisions 1 2013-01-01 2012-01-01 true Federal Register. 12.1 Section 12.1 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS OFFICIAL DISTRIBUTION WITHIN FEDERAL GOVERNMENT § 12.1 Federal Register. (a) Copies of the...

  14. Federal Communications Commission Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... Part XVIII Federal Communications Commission Semiannual Regulatory Agenda ] FEDERAL COMMUNICATIONS COMMISSION (FCC) FEDERAL COMMUNICATIONS COMMISSION 47 CFR Ch. I Unified Agenda of Federal Regulatory and Deregulatory Actions AGENCY: Federal Communications Commission. ACTION: Semiannual regulatory agenda. SUMMARY: Twice a year, in spring and...

  15. Mitigating earthquakes; the federal role

    USGS Publications Warehouse

    Press, F.

    1977-01-01

    With rapid approach of a capability to make reliable earthquake forecasts, it essential that the Federal Government play a strong, positive role in formulating and implementing plans to reduce earthquake hazards. Many steps are being taken in this direction, with the President looking to the Office of Science and Technology Policy (OSTP) in his Executive Office to provide leadership in establishing and coordinating Federal activities. 

  16. Federal Renewable Energy Screening Assistant

    SciTech Connect

    Shelpuk, B; Walker, A

    1994-10-01

    The Federal Renewable Energy Screening Assistant is a software tool to be used by energy auditors to prioritize future studies of potentially cost-effective renewable energy applications at federal facilities. This paper describes the structure and function of the tool, gives an inventory of renewable energy technologies represented in the tool, and briefly describes the algorithms used to rank opportunities by the savings-to-investment ratio.

  17. Federal Contractors and Sticky Costs

    DTIC Science & Technology

    2014-11-05

    NPS-CM-14-188 ACQUISITION RESEARCH PROGRAM SPONSORED REPORT SERIES Federal Contractors and Sticky Costs 5 November 2014 Stephen C. Hansen...average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed...Public Policy - iv - Naval Postgraduate School NPS-CM-14-188 Acquisition Research Program Sponsored Report Series Federal Contractors and

  18. Federal technology policy in transition

    SciTech Connect

    Carnes, K.H.

    1995-12-31

    This paper discusses federal energy and environmental policies and their impact on the U.S. economy. A brief history of the federal government`s role in developing scientific and technological infrastructure is given. Current trends in technology are summarized, with an emphasis on global aspects, and their impact on the economy is discussed. The need for a national technology policy, including continued research and development funding, is discussed and key elements of such a policy are outlined.

  19. ‘N-of-1- pathways ’ unveils personal deregulated mechanisms from a single pair of RNA-Seq samples: Towards precision medicine

    SciTech Connect

    Gardeux, Vincent; Achour, Ikbel; Li, Jianrong; Maienschein-Cline, Mark; Li, Haiquan; Pesce, Lorenzo; Parinandi, Gurunadh; Bahroos, Neil; Winn, Robert; Garcia, Joe G. N.; Foster, Ian; Lussier, Yves A.

    2014-11-01

    Background: The emergence of precision medicine allowed the incorporation of individual molecular data into patient care. This research entails, DNA sequencing predicts somatic mutations in individual patients. However, these genetic features overlook dynamic epigenetic and phenotypic response to therapy. Meanwhile, accurate personal transcriptome interpretation remains an unmet challenge. Further, N-of-1 (single-subject) efficacy trials are increasingly pursued, but are underpowered for molecular marker discovery. Method: ‘N-of-1-pathways’ is a global framework relying on three principles: (i) the statistical universe is a single patient; (ii) significance is derived from geneset/biomodules powered by paired samples from the same patient; and (iii) similarity between genesets/biomodules assesses commonality and differences, within-study and cross-studies. Thus, patient gene-level profiles are transformed into deregulated pathways. From RNA-Seq of 55 lung adenocarcinoma patients, N-of-1-pathways predicts the deregulated pathways of each patient. Results: Cross-patient N-of-1-pathways obtains comparable results with conventional genesets enrichment analysis (GSEA) and differentially expressed gene (DEG) enrichment, validated in three external evaluations. Moreover, heatmap and star plots highlight both individual and shared mechanisms ranging from molecular to organ-systems levels (eg, DNA repair, signaling, immune response). Patients were ranked based on the similarity of their deregulated mechanisms to those of an independent gold standard, generating unsupervised clusters of diametric extreme survival phenotypes (p=0.03). Conclusions: The N-of-1-pathways framework provides a robust statistical and relevant biological interpretation of individual disease-free survival that is often overlooked in conventional cross-patient studies. It enables mechanism-level classifiers with smaller cohorts as well as N-of-1 studies.

  20. ‘N-of-1- pathways ’ unveils personal deregulated mechanisms from a single pair of RNA-Seq samples: Towards precision medicine

    DOE PAGES

    Gardeux, Vincent; Achour, Ikbel; Li, Jianrong; ...

    2014-11-01

    Background: The emergence of precision medicine allowed the incorporation of individual molecular data into patient care. This research entails, DNA sequencing predicts somatic mutations in individual patients. However, these genetic features overlook dynamic epigenetic and phenotypic response to therapy. Meanwhile, accurate personal transcriptome interpretation remains an unmet challenge. Further, N-of-1 (single-subject) efficacy trials are increasingly pursued, but are underpowered for molecular marker discovery. Method: ‘N-of-1-pathways’ is a global framework relying on three principles: (i) the statistical universe is a single patient; (ii) significance is derived from geneset/biomodules powered by paired samples from the same patient; and (iii) similarity between genesets/biomodulesmore » assesses commonality and differences, within-study and cross-studies. Thus, patient gene-level profiles are transformed into deregulated pathways. From RNA-Seq of 55 lung adenocarcinoma patients, N-of-1-pathways predicts the deregulated pathways of each patient. Results: Cross-patient N-of-1-pathways obtains comparable results with conventional genesets enrichment analysis (GSEA) and differentially expressed gene (DEG) enrichment, validated in three external evaluations. Moreover, heatmap and star plots highlight both individual and shared mechanisms ranging from molecular to organ-systems levels (eg, DNA repair, signaling, immune response). Patients were ranked based on the similarity of their deregulated mechanisms to those of an independent gold standard, generating unsupervised clusters of diametric extreme survival phenotypes (p=0.03). Conclusions: The N-of-1-pathways framework provides a robust statistical and relevant biological interpretation of individual disease-free survival that is often overlooked in conventional cross-patient studies. It enables mechanism-level classifiers with smaller cohorts as well as N-of-1 studies.« less

  1. Common deregulated gene expression profiles and morphological changes in developing zebrafish larvae exposed to environmental-relevant high to low concentrations of glucocorticoids.

    PubMed

    Chen, Qiyu; Li, Caixia; Gong, Zhiyuan; Chan, Eric Chun Yong; Snyder, Shane A; Lam, Siew Hong

    2017-04-01

    Synthetic glucocorticoids have been detected in environmental waters and their biological potency have raised concerns of their impact on aquatic vertebrates especially fish. In this study, developing zebrafish larvae exposed to representative glucocorticoids (dexamethasone, prednisolone and triamcinolone) at 50 pM to 50 nM from 3 h post-fertilisation to 5 days post-fertilisation were investigated. Microarray analysis identified 1255, 1531, and 2380 gene probes, which correspondingly mapped to 660, 882 and 1238 human/rodent homologs, as deregulated by dexamethasone, prednisolone and triamcinolone, respectively. A total of 248 gene probes which mapped to 159 human/rodent homologs were commonly deregulated by the three glucocorticoids. These homologs were associated with over 20 molecular functions from cell cycle to cellular metabolisms, and were involved in the development and function of connective tissue, nervous, haematological, and digestive systems. Glucocorticoid receptor signalling, NRF2-mediated oxidative stress response and RAR signalling were among the top perturbed canonical pathways. Morphological analyses using four transgenic zebrafish lines revealed that the hepatic and endothelial-vascular systems were affected by all three glucocorticoids while nervous, pancreatic and myeloid cell systems were affected by one of them. Quantitative real-time PCR detected significant change in the expression of seven genes at 50 pM of all three glucocorticoids, a concentration comparable to total glucocorticoids reported in environmental waters. Three genes (cry2b, fbxo32, and klhl38b) responded robustly to all glucocorticoid concentrations tested. The common deregulated genes with the associated biological processes and morphological changes can be used for biological inference of glucocorticoid exposure in fish for future studies.

  2. Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water

    SciTech Connect

    Muñoz, Alexandra; Chervona, Yana; Hall, Megan; Kluz, Thomas; Gamble, Mary V.; Costa, Max

    2015-05-01

    Arsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung and bladder cancers, and cardiovascular disease. Recent research indicates that arsenic may be an endocrine disruptor. This study was conducted to evaluate the nature of gene expression changes among males and females exposed to arsenic contaminated water in Bangladesh at high and low doses. Twenty-nine (55% male) Bangladeshi adults with water arsenic exposure ranging from 50 to 1000 μg/L were selected from the Folic Acid Creatinine Trial. RNA was extracted from peripheral blood mononuclear cells for gene expression profiling using Affymetrix 1.0 ST arrays. Differentially expressed genes were assessed between high and low exposure groups for males and females separately and findings were validated using quantitative real-time PCR. There were 534 and 645 differentially expressed genes (p < 0.05) in the peripheral blood mononuclear cells of males and females, respectively, when high and low water arsenic exposure groups were compared. Only 43 genes overlapped between the two sexes, with 29 changing in opposite directions. Despite the difference in gene sets both males and females exhibited common biological changes including deregulation of 17β-hydroxysteroid dehydrogenase enzymes, deregulation of genes downstream of Sp1 (specificity protein 1) transcription factor, and prediction of estrogen receptor alpha as a key hub in cardiovascular networks. Arsenic-exposed adults exhibit sex-specific gene expression profiles that implicate involvement of the endocrine system. Due to arsenic's possible role as an endocrine disruptor, exposure thresholds for arsenic may require different parameters for males and females. - Highlights: • Males and females exhibit unique gene expression changes in response to arsenic. • Only 23 genes are common among the differentially expressed genes for the sexes. • Male and female gene lists exhibit common biological

  3. Federal Utility Program Overview (Fact Sheet)

    SciTech Connect

    Not Available

    2009-07-01

    Fact sheet overview of the U.S. Department of Energy (DOE) Federal Energy Management Program's (FEMP) Federal Utility Program, including common contracts and services available to Federal agencies through local serving utilities.

  4. Final Federal Radon Action Plan Scorecard

    EPA Pesticide Factsheets

    This page provides information and a link to the draft Federal Radon Action Plan. It also contains a Federal Radon Action Plan Scorecard, a tool designed to display the current status of each federal agency commitments and outcomes to date.

  5. 75 FR 6433 - Federal Aviation Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-09

    ... Federal Aviation Administration Notice of Availability of a Draft Environmental Assessment and Public...: Federal Aviation Administration (FAA), DOT. ACTION: Notice of Availability of a Draft Environmental... Chicago, Illinois. SUMMARY: The Federal Aviation Administration (FAA) proposes to fund, construct,...

  6. 76 FR 78966 - Federal Aviation Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-20

    ... Federal Aviation Administration Approval of Noise Compatibility Program for Kona International Airport at Keahole, Keahole, North Kona, HI AGENCY: Federal Aviation Administration, DOT. ACTION: Notice. SUMMARY: The Federal Aviation Administration (FAA) announces its findings on the noise compatibility...

  7. 76 FR 2745 - Federal Aviation Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Eighty-Fourth Meeting: RTCA Special Committee 159: Global Positioning System (GPS) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of RTCA Special...

  8. 78 FR 25337 - Federal Aviation Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Agency Information Collection Activities: Requests for Comments; Clearance of Renewed Approval of Information Collection: Operations Specifications AGENCY: Federal...

  9. 77 FR 64837 - Federal Aviation Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-23

    ... Federal Aviation Administration Fourth Meeting: RTCA Special Committee 227, Standards of Navigation Performance AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION... 15, 2012. Kathy Hitt, Management Analyst, Business Operations Group, Federal Aviation...

  10. 77 FR 58817 - Notice of Proposed Information Collection Requests; Federal Student Aid; Federal Family...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-24

    ... administrative requirements of the Federal Family Education Loan (FFEL) program. The information collection... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Notice of Proposed Information Collection Requests; Federal Student Aid; Federal Family Educational...

  11. Federal Resources for Sustainable Rural Communities

    EPA Pesticide Factsheets

    Federal Resources for Sustainable Rural Communities (2012) highlights federal resources rural communities can use to promote economic competitiveness, protect healthy environments, and enhance quality of life.

  12. 30 CFR 900.13 - Federal programs and Federal coal exploration programs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Federal programs and Federal coal exploration... INTRODUCTION § 900.13 Federal programs and Federal coal exploration programs. The rules for each Federal program and Federal coal exploration program are codified below under the assigned part for the...

  13. 30 CFR 900.13 - Federal programs and Federal coal exploration programs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Federal programs and Federal coal exploration... INTRODUCTION § 900.13 Federal programs and Federal coal exploration programs. The rules for each Federal program and Federal coal exploration program are codified below under the assigned part for the...

  14. 30 CFR 900.13 - Federal programs and Federal coal exploration programs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Federal programs and Federal coal exploration... INTRODUCTION § 900.13 Federal programs and Federal coal exploration programs. The rules for each Federal program and Federal coal exploration program are codified below under the assigned part for the...

  15. 30 CFR 900.13 - Federal programs and Federal coal exploration programs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Federal programs and Federal coal exploration... INTRODUCTION § 900.13 Federal programs and Federal coal exploration programs. The rules for each Federal program and Federal coal exploration program are codified below under the assigned part for the...

  16. 30 CFR 900.13 - Federal programs and Federal coal exploration programs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Federal programs and Federal coal exploration... INTRODUCTION § 900.13 Federal programs and Federal coal exploration programs. The rules for each Federal program and Federal coal exploration program are codified below under the assigned part for the...

  17. Deregulation of Rb-E2F1 Axis Causes Chromosomal Instability by Engaging the Transactivation Function of Cdc20–Anaphase-Promoting Complex/Cyclosome

    PubMed Central

    Nath, Somsubhra; Chowdhury, Abhishek; Dey, Sanjib; Roychoudhury, Anirban; Ganguly, Abira; Bhattacharyya, Dibyendu

    2014-01-01

    The E2F family of transcription factors regulates genes involved in various aspects of the cell cycle. Beyond the well-documented role in G1/S transition, mitotic regulation by E2F has also been reported. Proper mitotic progression is monitored by the spindle assembly checkpoint (SAC). The SAC ensures bipolar separation of chromosomes and thus prevents aneuploidy. There are limited reports on the regulation of the SAC by E2F. Our previous work identified the SAC protein Cdc20 as a novel transcriptional regulator of the mitotic ubiquitin carrier protein UbcH10. However, none of the Cdc20 transcription complex proteins have any known DNA binding domain. Here we show that an E2F1-DP1 heterodimer is involved in recruitment of the Cdc20 transcription complex to the UBCH10 promoter and in transactivation of the gene. We further show that inactivation of Rb can facilitate this transactivation process. Moreover, this E2F1-mediated regulation of UbcH10 influences mitotic progression. Deregulation of this pathway results in premature anaphase, chromosomal abnormalities, and aneuploidy. We conclude that excess E2F1 due to Rb inactivation recruits the complex of Cdc20 and the anaphase-promoting complex/cyclosome (Cdc20-APC/C) to deregulate the expression of UBCH10, leading to chromosomal instability in cancer cells. PMID:25368385

  18. Differential antioxidant defense and detoxification mechanisms in photodynamically stressed rice plants treated with the deregulators of porphyrin biosynthesis, 5-aminolevulinic acid and oxyfluorfen.

    PubMed

    Phung, Thu-Ha; Jung, Sunyo

    2015-04-03

    This study focuses on differential molecular mechanisms of antioxidant and detoxification systems in rice plants under two different types of photodynamic stress imposed by porphyrin deregulators, 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). The ALA-treated plants with white necrosis exhibited a greater decrease in photochemical quantum efficiency, Fv/Fm, as well as a greater increase in activity of superoxide dismutase, compared to the OF-treated plants. By contrast, the brown necrosis in OF-treated plants resulted in not only more widely dispersed H2O2 production and greater increases in H2O2-decomposing enzymes, catalase and peroxidase, but also lower ascorbate redox state. In addition, ALA- and OF-treated plants markedly up-regulated transcript levels of genes involved in detoxification processes including transport and movement, cellular homeostasis, and xenobiotic conjugation, with prominent up-regulation of serine/threonine kinase and chaperone only in ALA-treated plants. Our results demonstrate that different photodynamic stress imposed by ALA and OF developed differential actions of antioxidant enzymes and detoxification. Particularly, detoxification system may play potential roles in plant protection against photodynamic stress imposed by porphyrin deregulators, thereby contributing to alleviation of photodynamic damage.

  19. MiR-424 and miR-155 deregulated expression in cytogenetically normal acute myeloid leukaemia: correlation with NPM1 and FLT3 mutation status

    PubMed Central

    2012-01-01

    Background MicroRNA have a central role in normal haematopoiesis and are deregulated in acute myeloid leukaemia (AML). The purpose of the study was to investigate by qRT-PCR the expression of miRNAs involved in myeloid differentiation (miR-424, miR-155, miR-223, miR-17-5p) in 48 patients with cytogenetically normal AML well characterized for NPM1 and/or FLT3 mutations. Three types of normalization were used for the data validation. Findings We found that miR-424 was down-modulated in AMLs with NPM1mutA regardless of FLT3 status. On the contrary, miR-155 showed up-regulation in patients with FLT3 internal tandem duplications (ITD) with or without NPM1 mutations. No significant associations were found by analyzing miR-223 and miR-17-5p in relation to FLT3 and NPM1 status. Conclusions This study supports the view that major genetic subsets of CN-AML are associated with distinct miRNA signatures and suggests that miR-424 and miR-155 deregulation is involved in the pathogenesis of CN-AML with NPM1 and FLT3-ITD mutations, respectively. PMID:22681934

  20. Mutations in the HECT domain of NEDD4L lead to AKT/mTOR pathway deregulation and cause periventricular nodular heterotopia

    PubMed Central

    Ivanova, Ekaterina; Schmucker, Stéphane; Drouot, Nathalie; Clayton-Smith, Jill; Pagnamenta, Alistair T.; Metcalfe, Kay.A.; Isidor, Bertrand; Louvier, Ulrike Walther; Poduri, Annapurna; Taylor, Jenny C.; Tilly, Peggy; Poirier, Karine; Saillour, Yoann; Lebrun, Nicolas; Stemmelen, Tristan; Rudolf, Gabrielle; Muraca, Giuseppe; Saintpierre, Benjamin; Elmorjani, Adrienne; Moïse, Martin; Weirauch, Nathalie Bednarek; Guerrini, Renzo; Boland, Anne; Olaso, Robert; Masson, Cecile; Tripathy, Ratna; Keays, David; Beldjord, Cherif; Nguyen, Laurent; Godin, Juliette; Kini, Usha; Nischké, Patrick; Deleuze, Jean-François; Bahi-Buisson, Nadia; Sumara, Izabela; Hinckelmann, Maria-Victoria; Chelly, Jamel

    2016-01-01

    Neurodevelopmental disorders with periventricular nodular heterotopia (PNH) are etiologically heterogeneous, and their genetic causes remain in many cases unknown. Here we show that missense mutations in the HECT domain of the E3 ubiquitin ligase NEDD4L lead to PNH associated with toes syndactyly, cleft palate and neurodevelopmental delay. Cellular and expression data showed a sensitivity of PNH-associated mutants to proteasome degradation. Moreover, in utero electroporation approach showed that PNH-related mutants and excess of wild type (WT) NEDD4L affect neurogenesis, neuronal positioning and terminal translocation. Further investigations, including rapamycin based experiments, revealed differential deregulation of pathways involved. Excess of WT NEDD4L leads to a disruption of Dab1 and mTORC1 pathways, while PNH-related mutations are associated with a deregulation of mTORC1 and AKT activities. Altogether, these data provide insights to better understand the critical role of NEDD4L in the regulation of mTOR pathways and their contributions in cortical development. PMID:27694961

  1. MicroRNAs 142-3p, miR-155 and miR-203 Are Deregulated in Gastric MALT Lymphomas Compared to Chronic Gastritis

    PubMed Central

    FERNÁNDEZ, CONCEPCIÓN; BELLOSILLO*, BEATRIZ; FERRARO, MARIANA; SEOANE, AGUSTÍN; SÁNCHEZ-GONZÁLEZ, BLANCA; PAIRET, SILVIA; PONS, AINA; BARRANCO, LUIS; VELA, MARÍA CARMEN; GIMENO, EVA; COLOMO, LLUÍS; BESSES, CARLES; NAVARRO*, ALFONS; SALAR*, ANTONIO

    2016-01-01

    Background: Over the last years, our knowledge on pathogenesis of gastric MALT lymphoma has greatly improved, but its morphological diagnosis is still hampered by overlapping histological features with advanced chronic gastritis. MicroRNAs are deregulated in lymphomas, but their role and usefulness in gastric MALT lymphoma has not been extensively investigated. Materials and Methods: We analyzed the expression of 384 miRNAs using TaqMan microRNA assay in a training series of 10 gastric MALT lymphomas, 3 chronic gastritis and 2 reactive lymph nodes. Then, significantly deregulated miRNAs were individually assessed by real-time PCR in a validation series of 16 gastric MALT lymphomas and 12 chronic gastritis. Results: Gastric MALT lymphoma is characterized by a specific miRNA expression profile. Among the differentially expressed miRNAs, a significant overexpression of miR-142-3p and miR-155 and down-regulation of miR-203 was observed in gastric MALT lymphoma when compared to chronic gastritis. Conclusion: miR-142-3p, miR-155 and miR-203 expression levels might be helpful biomarkers for the differential diagnosis between gastric MALT lymphomas and chronic gastritis. *These Authors contributed equally to this study. PMID:28031239

  2. Evaluation on Influence of Unstable Primary-Energy Price in a Deregulated Electric Power Market—Analysis based on a simulation model approach—

    NASA Astrophysics Data System (ADS)

    Maitani, Tatsuyuki; Tezuka, Tetsuo

    The electric power market of Japan has been locally monopolized for a long time. But, like many countries, Japan is moving forward with the deregulation of its electric power industry so that any power generation company could sell electric power in the market. The power price, however, will fluctuate inevitably to balance the power supply and demand. A new appropriate market design is indispensable when introducing new market mechanisms in the electric power market to avoid undesirable results of the market. The first stage of deregulation will be the competition between an existing large-scaled power utility and a new power generation company. In this paper we have investigated the wholesale market with competition of these two power companies based on a simulation model approach. Under the competitive situation the effects of exogenous disturbance may bring serious results and we estimated the influence on the market when the price of fossil fuel rises. The conclusion of this study is that several types of Nash equilibriums have been found in the market: the larger the new power generation company becomes, the higher the electricity price under the Nash equilibriums rises. Because of the difference in their structure of generation capacity, the existing large-scaled power utility gets more profit while the new power generation company loses its profit when the price of fossil fuel rises.

  3. NASA's Secured Advanced Federated Environment

    NASA Technical Reports Server (NTRS)

    Chow, Edward; Korsmeyer, David; Paterson, Pat; Liu, Joseph; Stewart, Helen; Burchell, Scott; Chang, Pat; Spence, Matt Chew; Viernes, Conan; Goforth, Andy; Billik, Shoshana; Wheeller, Bob

    2003-01-01

    In 1999, a NASA-wide team initially set out to create a collaborative environment to enable NASA's scientists and engineers to share information and tools across NASA locations and with world-wide partners. This paper describes the team's development process and solutions in resolving conflicting security issues of building a complex intra/inter-enterprise collaborative system. Based on the federated, hierarchical, compartmentalized principles, the Secured Advanced Federated Environment (SAFE) developed by the team is becoming a foundational element for building a collaborative infrastructure for NASA. This paper also introduces the concept of a Micro Security Domain which can achieve the balance between the need to collaborate and the need to enforce enterprise and local security rules. SAFE'S federated security concepts enables networks to be formed around the functional/security requirements. With the SAFE technologies and approaches, security will not be an afterthought of the enterprise network design.

  4. Reluctant partners: Implementing federal policy

    SciTech Connect

    Stoker, R.P.

    1991-01-01

    Reluctant Partners examines how the federal government can secure the cooperation it needs to effect national policy goals whtn the implementation process itself empowers potential adversaries. The current battle over how and where to permanently store the nation's high-level nuclear waste poses one of the greatest challenges to federalism since the Civil War. Authority has been legislatively diffused among the federal government, the states, the counties, and certain affected Indian tribes. The situation also epitomizes the conflict that arises when Congress delegates final decisionmaking authority to the bureaucracy. The book contributes to the body of implementation literature by moving past organizational theory to consider issues of governance and leadership. However, it will disappoint the empiricist who sees an opportunity for the application of a theory go by the boards.

  5. Federal budget process: An overview

    NASA Astrophysics Data System (ADS)

    Frizzell, Virgil A., Jr.

    Much geophysical research funding originates from the federal government, and many who obtain federal funding consider the executive branch to be its source. In fact, the federal budget results from a complex ballet between the executive and legislative branches. Because it is both little understood and essential to our work, this report will review the fundamentals of the three-year budgetary process.The Constitution assigns the power of the purse to the Congress. Before the 1920s, executive branch agencies and departments submitted their own separate budgets to Congress, and deliberate planning and priority setting was minimal. In 1921 Congress empowered the president to submit an executive branch budget reflecting his priorities for the next fiscal year. Following this protocol, former President Reagan submitted his budget for Fiscal Year 1990 in January, and President Bush outlined his FY'90 priorities in February.

  6. Federal Personnel: Federal/Private Sector Pay Comparisons

    DTIC Science & Technology

    1994-12-01

    Federal Employees Covered by Social Security, December 1984. ^This finding is based on a comparison of employer cost associated with the various...and gender. Specifically, ’For a further discussion, see Robert Willis, "Wage Determinante : A Survey and ReinterpreteÜori of Human Capital Earnings

  7. Veterans Benefits: Federal Employment Assistance

    DTIC Science & Technology

    2007-05-25

    and the VWIP program, the VETS office in DOL also: CRS-4 7 Local one - stop service centers can be found online at [http://www.servicelocator.org/]. 8...USERRA, P.L. 103-353). All VETS activities are required partners in the One - Stop Career Center system established by WIA.7 Federal Employment...required to post job openings through state job services or one stop offices, and may post job openings on the federal online service (America’s Job Bank

  8. 40 CFR 1508.12 - Federal agency.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Federal agency. 1508.12 Section 1508.12 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY TERMINOLOGY AND INDEX § 1508.12 Federal agency. Federal agency means all agencies of the Federal Government. It does not mean the Congress,...

  9. 1 CFR 11.2 - Federal Register.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 1 General Provisions 1 2011-01-01 2011-01-01 false Federal Register. 11.2 Section 11.2 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS SUBSCRIPTIONS § 11.2 Federal Register. (a) The subscription price for the paper edition of...

  10. 1 CFR 12.1 - Federal Register.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Federal Register. 12.1 Section 12.1 General... PUBLICATIONS OFFICIAL DISTRIBUTION WITHIN FEDERAL GOVERNMENT § 12.1 Federal Register. (a) Copies of the daily Federal Register in paper or microfiche form shall be made available to the following without charge:...

  11. 1 CFR 11.2 - Federal Register.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Federal Register. 11.2 Section 11.2 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS SUBSCRIPTIONS § 11.2 Federal Register. (a) The subscription price for the paper edition of...

  12. 1 CFR 12.1 - Federal Register.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 1 General Provisions 1 2011-01-01 2011-01-01 false Federal Register. 12.1 Section 12.1 General... PUBLICATIONS OFFICIAL DISTRIBUTION WITHIN FEDERAL GOVERNMENT § 12.1 Federal Register. (a) Copies of the daily Federal Register in paper or microfiche form shall be made available to the following without charge:...

  13. 1 CFR 11.2 - Federal Register.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 1 General Provisions 1 2014-01-01 2012-01-01 true Federal Register. 11.2 Section 11.2 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS SUBSCRIPTIONS § 11.2 Federal Register. (a) The subscription price for the paper edition of...

  14. 1 CFR 11.2 - Federal Register.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 1 General Provisions 1 2012-01-01 2012-01-01 false Federal Register. 11.2 Section 11.2 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS SUBSCRIPTIONS § 11.2 Federal Register. (a) The subscription price for the paper edition of...

  15. 1 CFR 11.2 - Federal Register.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 1 General Provisions 1 2013-01-01 2012-01-01 true Federal Register. 11.2 Section 11.2 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS SUBSCRIPTIONS § 11.2 Federal Register. (a) The subscription price for the paper edition of...

  16. 77 FR 59026 - Federal Salary Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-25

    ... MANAGEMENT Federal Salary Council AGENCY: Office of Personnel Management. ACTION: Notice of meeting. SUMMARY: The Federal Salary Council will meet on October 19, 2012, at the time and location shown below. The... locality pay areas, the coverage of salary surveys, the process of comparing Federal and non-Federal...

  17. 78 FR 65717 - Federal Salary Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-01

    ... MANAGEMENT Federal Salary Council AGENCY: Office of Personnel Management. ACTION: Notice of meeting. SUMMARY: The Federal Salary Council meeting originally scheduled for November 5, 2013 (FR Vol. 78, No. 192... locality pay areas, the coverage of salary surveys, the process of comparing Federal and non-Federal...

  18. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false 2 Federal Special Federal Aviation Regulation No. 50 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Special Federal Aviation Regulation No....

  19. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false 2 Federal Special Federal Aviation Regulation No. 100 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... Federal Aviation Regulation No. 100-2 Editorial Note: For the text of SFAR No. 100-2, see part 61 of...

  20. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false 2 Federal Special Federal Aviation Regulation No. 50 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... Federal Aviation Regulation No. 50-2 Editorial Note: For the text of SFAR No. 50-2, see part 91 of...

  1. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false 2 Federal Special Federal Aviation Regulation No. 50 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... Federal Aviation Regulation No. 50-2 Editorial Note: For the text of SFAR No. 50-2, see part 91 of...

  2. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false 2 Federal Special Federal Aviation Regulation No. 100 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN CERTIFICATION: FLIGHT CREWMEMBERS OTHER THAN PILOTS Special Federal Aviation Regulation...

  3. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false 2 Federal Special Federal Aviation Regulation No. 50 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... Federal Aviation Regulation No. 50-2 Editorial Note: For the text of SFAR No. 50-2, see part 91 of...

  4. 14 CFR Special Federal Aviation... - 1

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false 1 Federal Special Federal Aviation Regulation No. 100 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN CERTIFICATION: AIRMEN OTHER THAN FLIGHT CREWMEMBERS Special Federal Aviation Regulation...

  5. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false 2 Federal Special Federal Aviation Regulation No. 100 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN CERTIFICATION: AIRMEN OTHER THAN FLIGHT CREWMEMBERS Special Federal Aviation Regulation...

  6. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false 2 Federal Special Federal Aviation Regulation No. 100 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN CERTIFICATION: AIRMEN OTHER THAN FLIGHT CREWMEMBERS Special Federal Aviation Regulation...

  7. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false 2 Federal Special Federal Aviation Regulation No. 50 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Special Federal Aviation Regulation No....

  8. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false 2 Federal Special Federal Aviation Regulation No. 100 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN CERTIFICATION: FLIGHT CREWMEMBERS OTHER THAN PILOTS Special Federal Aviation Regulation...

  9. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false 2 Federal Special Federal Aviation Regulation No. 100 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... Federal Aviation Regulation No. 100-2 Editorial Note: For the text of SFAR No. 100-2, see part 61 of...

  10. 14 CFR Special Federal Aviation... - 1

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false 1 Federal Special Federal Aviation Regulation No. 100 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN CERTIFICATION: FLIGHT CREWMEMBERS OTHER THAN PILOTS Special Federal Aviation Regulation...

  11. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false 2 Federal Special Federal Aviation Regulation No. 50 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Special Federal Aviation Regulation No....

  12. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false 2 Federal Special Federal Aviation Regulation No. 50 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... Federal Aviation Regulation No. 50-2 Editorial Note: For the text of SFAR No. 50-2, see part 91 of...

  13. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false 2 Federal Special Federal Aviation Regulation No. 50 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Special Federal Aviation Regulation No....

  14. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false 2 Federal Special Federal Aviation Regulation No. 50 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... Federal Aviation Regulation No. 50-2 Editorial Note: For the text of SFAR No. 50-2, see part 91 of...

  15. 14 CFR Special Federal Aviation... - 2

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false 2 Federal Special Federal Aviation Regulation No. 50 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Special Federal Aviation Regulation No....

  16. 23 CFR 751.17 - Federal participation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Federal participation. 751.17 Section 751.17 Highways... AND ACQUISITION § 751.17 Federal participation. (a) Federal funds may participate in 75 percent of the... Interstate and primary highways, the FHWA may approve Federal participation in the costs of applying...

  17. 23 CFR 772.13 - Federal participation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Federal participation. 772.13 Section 772.13 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT PROCEDURES FOR ABATEMENT OF HIGHWAY TRAFFIC NOISE AND CONSTRUCTION NOISE § 772.13 Federal participation. (a) Federal...

  18. 23 CFR 772.13 - Federal participation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Federal participation. 772.13 Section 772.13 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT PROCEDURES FOR ABATEMENT OF HIGHWAY TRAFFIC NOISE AND CONSTRUCTION NOISE § 772.13 Federal participation. (a) Federal...

  19. 23 CFR 751.17 - Federal participation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Federal participation. 751.17 Section 751.17 Highways... AND ACQUISITION § 751.17 Federal participation. (a) Federal funds may participate in 75 percent of the... Interstate and primary highways, the FHWA may approve Federal participation in the costs of applying...

  20. 23 CFR 752.11 - Federal participation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Federal participation. 752.11 Section 752.11 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT LANDSCAPE AND ROADSIDE DEVELOPMENT § 752.11 Federal participation. (a) Federal-aid highway funds, but generally...

  1. 49 CFR 1325.3 - Federal office.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Federal office. 1325.3 Section 1325.3... FEDERAL OFFICE OR THEIR REPRESENTATIVES § 1325.3 Federal office. For the purposes of this section, Federal office means the office of President or Vice President of the United States; or of Senator...

  2. 23 CFR 751.17 - Federal participation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 23 Highways 1 2014-04-01 2014-04-01 false Federal participation. 751.17 Section 751.17 Highways... AND ACQUISITION § 751.17 Federal participation. (a) Federal funds may participate in 75 percent of the... Interstate and primary highways, the FHWA may approve Federal participation in the costs of applying...

  3. 23 CFR 752.11 - Federal participation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 23 Highways 1 2014-04-01 2014-04-01 false Federal participation. 752.11 Section 752.11 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT LANDSCAPE AND ROADSIDE DEVELOPMENT § 752.11 Federal participation. (a) Federal-aid highway funds, but generally...

  4. 23 CFR 751.17 - Federal participation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 23 Highways 1 2013-04-01 2013-04-01 false Federal participation. 751.17 Section 751.17 Highways... AND ACQUISITION § 751.17 Federal participation. (a) Federal funds may participate in 75 percent of the... Interstate and primary highways, the FHWA may approve Federal participation in the costs of applying...

  5. 23 CFR 752.11 - Federal participation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 23 Highways 1 2013-04-01 2013-04-01 false Federal participation. 752.11 Section 752.11 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT LANDSCAPE AND ROADSIDE DEVELOPMENT § 752.11 Federal participation. (a) Federal-aid highway funds, but generally...

  6. 23 CFR 752.11 - Federal participation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 23 Highways 1 2012-04-01 2012-04-01 false Federal participation. 752.11 Section 752.11 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT LANDSCAPE AND ROADSIDE DEVELOPMENT § 752.11 Federal participation. (a) Federal-aid highway funds, but generally...

  7. Federal Involvement in Day Care.

    ERIC Educational Resources Information Center

    Malone, Margaret

    Because of the expanding need for child care for preschool children, and for older children in after-school hours, there is greater interest in programs for day care, and increasing acceptance of the concept of publicly-financed day care. This paper describes the market for day care, the federal programs which exist and the standards which have…

  8. Federal Financing of Indian Education.

    ERIC Educational Resources Information Center

    Loon, Eric Van

    Since over 200 million Federal dollars are disbursed annually for American Indian education under Bureau of Indian Affairs (BIA), Elementary Secondary Education Act Title I, Indian Education Act Title IV, and Johnson O'Malley programs, it is difficult to understand the dismal state of Indian education. However, factors contributing to abuse of…

  9. Federal Supervisors and Poor Performers

    DTIC Science & Technology

    1999-07-01

    This report looks at the prevalence of poor performance in the Federal workplace from the perspective of employees and supervisors. The report also...examines what supervisors do about poor performers, the effects of supervisors’ actions, and the factors that influence supervisors’ decisions about how they will handle inadequate performance.

  10. The Universities and Federal Regulation.

    ERIC Educational Resources Information Center

    Crowley, John C.

    The impact of increasing federal regulation on American universities is discussed based on an informal survey of senior academic and administrative officials in 13 public and private universities. As government regulation is becoming more intensive and compliance more resource- and time-consuming, government is perceived as having little…

  11. Teacher Leadership: Federal Policy Recommendations

    ERIC Educational Resources Information Center

    Gran, Jackie; Young, Margaret; Broin, Alexandra

    2015-01-01

    This policy brief was developed specifically for federal policymakers, and builds upon the policy recommendations included in "Leading from Every Seat: Empowering Principals to Cultivate Teacher Leadership for School Improvement." The recommendations in this report include the following: (1) Uncover New Leadership Ideas and Seed…

  12. Guide to Federal Consumer Services.

    ERIC Educational Resources Information Center

    Office of Consumer Affairs, Washington, DC.

    This publication lists the consumer services of every Federal agency or bureau that is either directly of indirectly concerned with consumer issues. Services covered include agricultural research service, consumer and marketing service, extension service, food and nutrition service, rural development and conservation, farm credit, environmental…

  13. Federalization of Education in Chihuahua

    ERIC Educational Resources Information Center

    Marak, Andrae M.

    2005-01-01

    This article examines the politics behind the initial centralization of primary education in Chihuahua, Mexico during the 1920s and 1930s. The article argues that the centralization of primary education was one of many tools used by the federal government to consolidate its power in the wake of the Mexican Revolution (1910-1917) and create a…

  14. Federal Advisory Committees: An Overview

    DTIC Science & Technology

    2009-04-16

    initiating a tradition of presidential use of outside expertise when, in 1794 , he appointed an ad hoc group of commissioners to investigate the Whiskey ... Rebellion .7 Since 1842, Congress has legislated control over federal advisory bodies — mostly by limiting funding and committee member pay. In 1842...reports aggregated advisory body information to Congress annually.12 7 " Whiskey Insurrection in

  15. The Federal Government and Nutrition.

    ERIC Educational Resources Information Center

    Powers, Margaret A.

    1980-01-01

    Both the Department of Agriculture and the Department of Health and Human Services conduct research related to food and human nutrition. Several federal programs supporting nutrition research and education are reviewed. Footnotes provide addresses and ways to obtain more detailed information about nutrition related programs. (JN)

  16. Federal Depository Libraries and Librarianship.

    ERIC Educational Resources Information Center

    Illinois Libraries, 1986

    1986-01-01

    Reports results of 1985 survey of federal depository libraries in Illinois, including the arrangement of collections and bibliographic access, acquisitions and weeding, services and equipment, library and librarian cooperation, documents staff, State Plan and State Plan Coordinating Council, online systems and access to government documents, and…

  17. Update: Federal Republic of Germany.

    ERIC Educational Resources Information Center

    Loewenthal, Nessa P.

    The Federal Republic of Germany is widely respected for its highly developed economy, rich cultural life, and significant contributions to science, mathematics, and the arts. Designed for families or individuals planning to move to or live in Germany for extended periods of time, this book provides guidance in such practical matters as entry…

  18. Green Roofs: Federal Energy Management Program (FEMP) Federal Technology Alert

    SciTech Connect

    Scholz-Barth, K.; Tanner, S.

    2004-09-01

    In a ''green roof,'' a layer of vegetation (e.g., a roof garden) covers the surface of a roof to provide shade, cooler indoor and outdoor temperatures, and effective storm-water management to reduce runoff. The main components are waterproofing, soil, and plants. There are two basic kinds: intensive and extensive. An intensive green roof often features large shrubs and trees, and it can be expensive to install and maintain. An extensive green roof features shallow soil and low-growing, horizontally spreading plants that can thrive in the alpine conditions of many rooftops. These plants do not require a lot of water or soil, and they can tolerate a significant amount of exposure to the sun and wind. This Federal Technology Alert focuses on the benefits, design, and implementation of extensive green roofs and includes criteria for their use on federal facilities.

  19. High Level Architecture (HLA) federation with Umbra and OPNET federates.

    SciTech Connect

    Oppel, Fred John III; Hart, Brian; Van Leeuwen, Brian P.

    2004-03-01

    Network-centric systems that depend on mobile wireless ad hoc networks for their information exchange require detailed analysis to support their development. In many cases, this critical analysis is best provided with high-fidelity system simulations that include the effects of network architectures and protocols. In this research, we developed a high-fidelity system simulation capability using an HLA federation. The HLA federation, consisting of the Umbra system simulator and OPNET Modeler network simulator, provides a means for the system simulator to both affect, and be affected by, events in the network simulator. Advances are also made in increasing the fidelity of the wireless communication channel and reducing simulation run-time with a dead reckoning capability. A simulation experiment is included to demonstrate the developed modeling and simulation capability.

  20. Deregulation of the California electric power industry: An analysis of electric and natural gas corporate mergers and their effect on the California electric power market

    NASA Astrophysics Data System (ADS)

    Hornbuckle, James Dixon

    Deregulation of the electric utility industry in California is moving in a direction that places greater reliance on the market forces of competition. Investor owned utilities (IOU's) are using mergers and acquisitions to improve their ability to compete in this new environment. Two large mergers were proposed in 1996 that could affect the California market. The first is between Enron Corporation, a large power marketer and Portland General Corporation, owner of Portland General Electric. The second is between Pacific Enterprises Inc., owner of Southern California Gas Company, the largest natural gas utility in the U. S., and Enova Corporation, owner of San Diego Gas and Electric Company. Understanding the impact of these mergers on the California electric power market is the focus of this study. This study examines hypotheses dealing with: (1) Merger Strategy, (2) Efficiency, and (3) Market Power. Using the Miles and Snow (1978) typology, I develop a strategic orientation model for the merger participants and their competitors. The results suggest a two-stage strategic orientation: (1) regulated core business stage, where the firms follow a Defender strategy, and (2) unregulated business stage, where the firms follow a Prospector strategy. Further, the results show the mergers are consistent with the strategy of Enron and Pacific Enterprises. Event study methodology, dollar gains/losses and market value weighted returns are used to determine if the mergers support the efficiency hypothesis. The evidence suggests the mergers lead to increased competitive advantage through improved efficiency for the participants. The results also suggest the mergers do not harm the rivals. The results of structural changes made by the California Public Utilities Commission (CPUC) in deregulation of the California market and analysis of the mergers by the CPUC and the Public Utility Commission of Oregon suggest that the exercise of market power is not a significant issue. Finally

  1. 49 CFR 613.300 - Coordination of Federal and federally assisted programs and projects.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Coordination of Federal and federally assisted programs and projects. 613.300 Section 613.300 Transportation Other Regulations Relating to Transportation... Coordination of Federal and Federally Assisted Programs and Projects § 613.300 Coordination of Federal...

  2. 75 FR 8278 - Participation by Federal Candidates and Officeholders at Non-Federal Fundraising Events

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-24

    ... 11 CFR Part 300 Participation by Federal Candidates and Officeholders at Non- Federal Fundraising... participation by Federal candidates and officeholders in non-Federal fundraising events, with a public hearing... rulemaking (``NPRM'') relating to participation by Federal candidates and officeholders in...

  3. The FY2011 Federal Budget

    DTIC Science & Technology

    2010-08-04

    Finance August 4, 2010 Congressional Research Service 7-5700 www.crs.gov R41097 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 The FY2011 Federal Budget Congressional Research Service Summary While considering the...current form may pass substantial economic burdens to future generations. The Obama Administration released its FY2011 budget on February 1, 2010. The

  4. The FY2011 Federal Budget

    DTIC Science & Technology

    2010-03-09

    Finance March 9, 2010 Congressional Research Service 7-5700 www.crs.gov R41097 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 The FY2011 Federal Budget Congressional Research Service Summary While considering the...current form may pass substantial economic burdens to future generations. The Obama Administration released its FY2011 budget on February 1, 2010

  5. Veterans Benefits: Federal Employment Assistance

    DTIC Science & Technology

    2010-04-09

    Services Employment and Reemployment Rights Act of 1994 (USERRA, P.L. 103-353). All VETS activities are required partners in the One - Stop Career Center...please see CRS Report RL34024, Veterans and Homelessness, by Libby Perl. 8 Local one - stop service centers can be found online at http...through state job services or one stop offices, and may post job openings on the federal online service (America’s Job Bank).15 Veterans Hiring

  6. Veterans Benefits: Federal Employment Assistance

    DTIC Science & Technology

    2008-01-14

    enhance workforce investment activities CRS-4 7 Local one - stop service centers can be found online at [http://www.servicelocator.org/]. 8 For federal...Employment and Reemployment Rights Act of 1994 (USERRA, P.L. 103-353). All VETS activities are required partners in the One - Stop Career Center system...veterans. Contractors and subcontractors are required to post job openings through state job services or one stop offices, and may post job openings

  7. Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water.

    PubMed

    Muñoz, Alexandra; Chervona, Yana; Hall, Megan; Kluz, Thomas; Gamble, Mary V; Costa, Max

    2015-05-01

    Arsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung and bladder cancers, and cardiovascular disease. Recent research indicates that arsenic may be an endocrine disruptor. This study was conducted to evaluate the nature of gene expression changes among males and females exposed to arsenic contaminated water in Bangladesh at high and low doses. Twenty-nine (55% male) Bangladeshi adults with water arsenic exposure ranging from 50 to 1000 μg/L were selected from the Folic Acid Creatinine Trial. RNA was extracted from peripheral blood mononuclear cells for gene expression profiling using Affymetrix 1.0 ST arrays. Differentially expressed genes were assessed between high and low exposure groups for males and females separately and findings were validated using quantitative real-time PCR. There were 534 and 645 differentially expressed genes (p<0.05) in the peripheral blood mononuclear cells of males and females, respectively, when high and low water arsenic exposure groups were compared. Only 43 genes overlapped between the two sexes, with 29 changing in opposite directions. Despite the difference in gene sets both males and females exhibited common biological changes including deregulation of 17β-hydroxysteroid dehydrogenase enzymes, deregulation of genes downstream of Sp1 (specificity protein 1) transcription factor, and prediction of estrogen receptor alpha as a key hub in cardiovascular networks. Arsenic-exposed adults exhibit sex-specific gene expression profiles that implicate involvement of the endocrine system. Due to arsenic's possible role as an endocrine disruptor, exposure thresholds for arsenic may require different parameters for males and females.

  8. Differential antioxidant defense and detoxification mechanisms in photodynamically stressed rice plants treated with the deregulators of porphyrin biosynthesis, 5-aminolevulinic acid and oxyfluorfen

    SciTech Connect

    Phung, Thu-Ha; Jung, Sunyo

    2015-04-03

    This study focuses on differential molecular mechanisms of antioxidant and detoxification systems in rice plants under two different types of photodynamic stress imposed by porphyrin deregulators, 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). The ALA-treated plants with white necrosis exhibited a greater decrease in photochemical quantum efficiency, F{sub v}/F{sub m}, as well as a greater increase in activity of superoxide dismutase, compared to the OF-treated plants. By contrast, the brown necrosis in OF-treated plants resulted in not only more widely dispersed H{sub 2}O{sub 2} production and greater increases in H{sub 2}O{sub 2}-decomposing enzymes, catalase and peroxidase, but also lower ascorbate redox state. In addition, ALA- and OF-treated plants markedly up-regulated transcript levels of genes involved in detoxification processes including transport and movement, cellular homeostasis, and xenobiotic conjugation, with prominent up-regulation of serine/threonine kinase and chaperone only in ALA-treated plants. Our results demonstrate that different photodynamic stress imposed by ALA and OF developed differential actions of antioxidant enzymes and detoxification. Particularly, detoxification system may play potential roles in plant protection against photodynamic stress imposed by porphyrin deregulators, thereby contributing to alleviation of photodynamic damage. - Highlights: • We employ two different types of photodynamic stress, white and brown necrosis. • We examine molecular mechanisms of antioxidative and detoxification systems. • ALA and OF develop differential actions of antioxidant and detoxification systems. • Coordinated mechanism of antioxidants and detoxification works against toxic ROS. • Detoxification system plays critical roles in protection against photodynamic stress.

  9. Deregulation of the hedgehog signalling pathway: a possible role for the PTCH and SUFU genes in human rhabdomyoma and rhabdomyosarcoma development.

    PubMed

    Tostar, Ulrica; Malm, Carl Johan; Meis-Kindblom, Jeanne M; Kindblom, Lars-Gunnar; Toftgård, Rune; Undén, Anne Birgitte

    2006-01-01

    The naevoid basal cell carcinoma syndrome (NBCCS) is caused by mutations in the hedgehog receptor PTCH gene. It is characterized by developmental defects and a predisposition to the development of certain tumours, such as basal cell carcinoma, medulloblastoma and meningioma, and potentially fetal rhabdomyomas and embryonal rhabdomyosarcomas. This study aimed to analyse PTCH status in an NBCCS patient with fetal rhabdomyoma and to investigate whether deregulation of hedgehog signalling, as shown by altered expression of hedgehog pathway components and/or genetic imbalances, is a general finding in sporadic rhabdomyomas and rhabdomyosarcomas. The NBCCS patient had a novel PTCH germ-line mutation, 1370insT, and developed a fetal rhabdomyoma that harboured a 30 bp in-frame deletion in the second allele resulting in homozygous inactivation of PTCH. Sporadic rhabdomyomas and rhabdomyosarcomas showed overexpression of PTCH (43/43) and GLI1 (41/43) mRNA, as determined by in situ hybridization, indicating ongoing active hedgehog signalling. Immunohistochemical staining revealed a subgroup of fetal rhabdomyomas and embryonal rhabdomyosarcomas (12/34) lacking PTCH immunoreactivity. Four of nine informative fetal rhabdomyomas and embryonal rhabdomyosarcomas showed loss of heterozygosity (LOH) in the PTCH region with two of these (one fetal rhabdomyoma and one embryonal rhabdomyosarcoma) also showing LOH in the SUFU region. These findings suggest that haploinsufficiency for the two tumour suppressor genes PTCH and SUFU, which are both active in the same signalling pathway, may be important for tumour development. Based on our results we propose that the pathogenesis of rhabdomyoblastic tumours, particularly fetal rhabdomyomas and embryonal rhabdomyosarcomas, involves deregulation of the hedgehog signalling pathway.

  10. Concentration of circulating miRNA-containing particles in serum enhances miRNA detection and reflects CRC tissue-related deregulations

    PubMed Central

    ElSharawy, Abdou; Röder, Christian; Becker, Thomas; Habermann, Jens K.; Schreiber, Stefan; Rosenstiel, Philip; Kalthoff, Holger

    2016-01-01

    The emerging potential of miRNAs as biomarkers for cancer detection demands parallel evaluation of strategies for reliable identification of disease-related signatures from easily accessible and pertinent body compartments. Here, we addressed whether efficient concentration of circulating miRNA-carrying particles is a rationale for miRNA biomarker discovery. We systematically compared miRNA signatures in 93 RNA preparations from three serum entities (whole serum, particle-concentrated, and particle-depleted fractions) and corresponding tissue samples from patients with colorectal cancer (CRC) as a model disease. Significant differences between whole sera and particle-concentrated serum fractions of CRC patients emerged for 45 of 742 tested miRNAs. Twenty-eight of these 45 miRNAs were differentially expressed between particle-concentrated serum fractions of metastatic CRC- and healthy individuals. Over half of these candidates (15 of 28) showed deregulations only in concentrated serum fractions, but not in whole sera, compared to the respective controls. Our results also provided evidence of a consistent downregulation of miR-486 and miR-92a, and further showed a possible “strand-specific” deregulation of extracellular miRNAs in CRC. More importantly, most of the identified miRNAs in the enriched sera reflected the patterns of the corresponding tumor tissues and showed links to cancer-related inflammation. Further investigation of seven serum pools revealed a subset of potential extracellular miRNA candidates to be implicated in both neoplastic and inflammatory bowel disease. Our findings demonstrate that enrichment and sensitive detection of miRNA carriers is a promising approach to detect CRC-related pathological changes in liquid biopsies, and has potential for clinical diagnostics. PMID:27683108

  11. Correlation Network Analysis Reveals Relationships between MicroRNAs, Transcription Factor T-bet, and Deregulated Cytokine/Chemokine-Receptor Network in Pulmonary Sarcoidosis

    PubMed Central

    Dyskova, Tereza; Fillerova, Regina; Novosad, Tomas; Kudelka, Milos; Zurkova, Monika; Gajdos, Petr; Kolek, Vitezslav; Kriegova, Eva

    2015-01-01

    Sarcoidosis is an inflammatory granulomatous disease with unknown etiology driven by cytokines and chemokines. There is limited information regarding the regulation of cytokine/chemokine-receptor network in bronchoalveolar lavage (BAL) cells in pulmonary sarcoidosis, suggesting contribution of miRNAs and transcription factors. We therefore investigated gene expression of 25 inflammation-related miRNAs, 27 cytokines/chemokines/receptors, and a Th1-transcription factor T-bet in unseparated BAL cells obtained from 48 sarcoidosis patients and 14 control subjects using quantitative RT-PCR. We then examined both miRNA-mRNA expressions to enrich relevant relationships. This first study on miRNAs in sarcoid BAL cells detected deregulation of miR-146a, miR-150, miR-202, miR-204, and miR-222 expression comparing to controls. Subanalysis revealed higher number of miR-155, let-7c transcripts in progressing (n = 20) comparing to regressing (n = 28) disease as assessed by 2-year follow-up. Correlation network analysis revealed relationships between microRNAs, transcription factor T-bet, and deregulated cytokine/chemokine-receptor network in sarcoid BAL cells. Furthermore, T-bet showed more pronounced regulatory capability to sarcoidosis-associated cytokines/chemokines/receptors than miRNAs, which may function rather as “fine-tuners” of cytokine/chemokine expression. Our correlation network study implies contribution of both microRNAs and Th1-transcription factor T-bet to the regulation of cytokine/chemokine-receptor network in BAL cells in sarcoidosis. Functional studies are needed to confirm biological relevance of the obtained relationships. PMID:26696750

  12. Findability of Federal Research Data

    NASA Astrophysics Data System (ADS)

    Hourcle, J. A.

    2013-12-01

    Findability of Federal Research Data Although many of the federal agencies have been providing access to scientific research data for years if not decades, the findability of the data has been quite lacking. Many discipline-wide efforts have been made in the big science communities, such as PDS for planetary science and the VOs in night time astronomy and heliophysics, but there is a lack of single entry point for someone looking for data. The science.gov website contains links to many of these big-science search systems, but doesn't differentiate between links to science quality data and websites or browse products, making it more difficult to search specifically for data. The data.gov website is a useful repository for PIs of small science data to stash their data, particularly as it allows for interested parties to interact with tabular data. Unfortunately, as each group thinks of their data differently, much of what's now in the system is a mess; collections of data being tracked as individual records with no relationships between them. Big science projects also get tracked as single records, potentially with only a single record for missions with multiple instruments and significantly different data series. We present recommendations on how to improve the findability of federal research data on data.gov, based on years of working on the Virtual Solar Observatory and withing the science informatics community.

  13. 78 FR 67200 - Federal-State Unemployment Compensation Program: Certifications for 2013 Under the Federal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ... Employment and Training Administration Federal-State Unemployment Compensation Program: Certifications for 2013 Under the Federal Unemployment Tax Act AGENCY: Employment and Training Administration. ACTION: Notice. SUMMARY: The Secretary of Labor signed the annual certifications under the Federal...

  14. 76 FR 54772 - Federal Management Regulation; FMR Bulletin PBS-2011-B2; Redesignations of Federal Buildings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-02

    ... ADMINISTRATION Federal Management Regulation; FMR Bulletin PBS-2011-B2; Redesignations of Federal Buildings AGENCY: Public Buildings Service (P), General Services Administration. ACTION: Notice of a bulletin. SUMMARY: The attached bulletin announces the designation and redesignation of two Federal...

  15. 48 CFR Appendix - Federal Acquisition Regulation (FAR) Index

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Federal Acquisition Regulation (FAR) Index Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT... (IFMS) Contract clause. FAR Index Federal Acquisition Regulation (FAR) Index Editorial Note:...

  16. 48 CFR Appendix - Federal Acquisition Regulation (FAR) Index

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Federal Acquisition Regulation (FAR) Index Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT... (IFMS) Contract clause. FAR Index Federal Acquisition Regulation (FAR) Index Editorial Note:...

  17. 78 FR 33092 - Federal Advisory Committee Act; Technological Advisory Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-03

    ... From the Federal Register Online via the Government Publishing Office FEDERAL COMMUNICATIONS COMMISSION Federal Advisory Committee Act; Technological Advisory Council AGENCY: Federal Communications..., this notice advises interested persons that the Federal Communications Commission's (FCC)...

  18. Federal laboratories for the 21st century

    SciTech Connect

    Gover, J.; Huray, P.G.

    1998-04-01

    Federal laboratories have successfully filled many roles for the public; however, as the 21st Century nears it is time to rethink and reevaluate how Federal laboratories can better support the public and identify new roles for this class of publicly-owned institutions. The productivity of the Federal laboratory system can be increased by making use of public outcome metrics, by benchmarking laboratories, by deploying innovative new governance models, by partnerships of Federal laboratories with universities and companies, and by accelerating the transition of federal laboratories and the agencies that own them into learning organizations. The authors must learn how government-owned laboratories in other countries serve their public. Taiwan`s government laboratory, Industrial Technology Research Institute, has been particularly successful in promoting economic growth. It is time to stop operating Federal laboratories as monopoly institutions; therefore, competition between Federal laboratories must be promoted. Additionally, Federal laboratories capable of addressing emerging 21st century public problems must be identified and given the challenge of serving the public in innovative new ways. Increased investment in case studies of particular programs at Federal laboratories and research on the public utility of a system of Federal laboratories could lead to increased productivity of laboratories. Elimination of risk-averse Federal laboratory and agency bureaucracies would also have dramatic impact on the productivity of the Federal laboratory system. Appropriately used, the US Federal laboratory system offers the US an innovative advantage over other nations.

  19. 41 CFR 101-29.502 - Use of Federal specifications and interim Federal specifications in Federal construction contracts.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....502 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND PROCUREMENT 29-FEDERAL PRODUCT DESCRIPTIONS 29.5-Use of and... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Use of...

  20. 77 FR 66087 - Federal Perkins Loan Program, Federal Family Education Loan Program, and William D. Ford Federal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-01

    ...The Secretary amends the Federal Perkins Loan (Perkins Loan) program, Federal Family Education Loan (FFEL) program, and William D. Ford Federal Direct Loan (Direct Loan) program regulations. These final regulations implement a new Income-Contingent Repayment (ICR) plan in the Direct Loan program based on the President's ``Pay As You Earn'' repayment initiative, incorporate recent statutory......

  1. 77 FR 28860 - Notice of Proposed Information Collection Requests; Federal Student Aid; Federal Perkins Loan...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-16

    ... Master Promissory Note SUMMARY: The Federal Perkins Loan Master Promissory Note (MPN) provides the terms... records. Title of Collection: Federal Perkins Loan Program Master Promissory Note. OMB Control...

  2. Federal Interagency Committee on Indoor Air Quality

    EPA Pesticide Factsheets

    The Federal Interagency Committee on Indoor Air Quality (CIAQ), which meets three times a year, was established by Congress to coordinate the activities of the Federal Government on issues relating to Indoor Air Quality.

  3. Enforcement and Compliance at Federal Facilities

    EPA Pesticide Factsheets

    Guide for complying with environmental laws and regulations at Federal Facilities This resource updates EPA's The Yellow Book: Guide to Environmental Enforcement and Compliance in Federal Facilities published in 1999.

  4. 77 FR 38342 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Week of June 25, 2012. PLACE: Commissioners' Conference Room, 11555 Rockville Pike, Rockville,...

  5. 77 FR 1521 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-10

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Weeks of January 9, 16, 23, 30, February 6, 13, 2012. PLACE: Commissioners' Conference Room,...

  6. 76 FR 8788 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ... From the Federal Register Online via the Government Publishing Office ] NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Weeks of February 14, 21, 28, March 7, 14, 21, 2011. PLACE: Commissioners' Conference Room,...

  7. 76 FR 10410 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-24

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY: Nuclear Regulatory Commission. DATES: Weeks of February 21, 28, March 7, 14, 21, 28, 2011. PLACE: Commissioners' Conference Room, 11555 Rockville...

  8. 77 FR 61644 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-10

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Weeks of October 8, 15, 22, 29, November 5, 12, 2012. PLACE: Commissioners' Conference Room,...

  9. 77 FR 5063 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission, DATE: Week of January 30, 2012. PLACE: Commissioners' Conference Room, 11555 Rockville Pike,...

  10. 77 FR 59678 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-28

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATES: Weeks of October 1, 8, 15, 22, 29, November 5, 2012. PLACE: Commissioners' Conference Room,...

  11. 77 FR 15142 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-14

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Week of March 12, 2012. PLACE: Commissioners' Conference Room, 11555 Rockville Pike,...

  12. 75 FR 80083 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-21

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATES: Weeks of December 20, 27, 2010, January 3, 10, 17, 24, 2011. PLACE: Commissioners' Conference...

  13. 77 FR 2572 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-18

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATES: Weeks of January 16, 23, 30, February 6, 13, 20, 2012. PLACE: Commissioners' Conference Room,...

  14. 76 FR 55718 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-08

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice Agency Holding The Meetings: Nuclear Regulatory Commission. DATE: Week of September 5, 2011. PLACE: Commissioners' Conference Room, 11555 Rockville Pike,...

  15. 76 FR 16459 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Week of March 21, 2011. PLACE: Commissioners' Conference Room, 11555 Rockville Pike,...

  16. 76 FR 46329 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-02

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Weeks of August 1, 8, 15, 22, 29, September 5, 2011. PLACE: Commissioners' Conference Room,...

  17. 75 FR 55832 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission [NRC-2010- 0002]. DATES: Weeks of September 13, 20, 27, October 4, 11, 18, 2010. PLACE:...

  18. 77 FR 17102 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-23

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission, [NRC-2012- 0002]. DATE: Week of March 26, 2012. PLACE: Commissioners' Conference Room, 11555 Rockville...

  19. 75 FR 64367 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-19

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission, DATE: Weeks of October 18, 25, November 1, 8, 15, 22, 2010. PLACE: Commissioners' Conference Room,...

  20. 77 FR 48564 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Weeks of August 13, 20, 27, September 3, 10, 17, 2012. PLACE: Commissioners' Conference Room,...

  1. 75 FR 62894 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-13

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice Agency Holding the Meetings: Nuclear Regulatory Commission. Date: Weeks of October 11, 18, 25, November 1, 8, 15, 2010. Place: Commissioners' Conference Room,...

  2. 75 FR 28303 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-20

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission, [NRC-2010- 0002]. DATE: Week of May 24, 2010. PLACE: Commissioners' Conference Room, 11555 Rockville...

  3. 77 FR 57597 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-18

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission, DATE: Weeks of September 17, 24, October 1, 8, 15, 22, 2012. PLACE: Commissioners' Conference Room,...

  4. 75 FR 34489 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ... From the Federal Register Online via the Government Publishing Office ] NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATES: Week of June 14, 2010. PLACE: Commissioners' Conference Room, 11555 Rockville Pike, Rockville,...

  5. 76 FR 52717 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. ] DATE: Weeks of August 22, 29, September 5, 12, 19, 26, 2011. PLACE: Commissioners' Conference...

  6. 76 FR 1653 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-11

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATES: Weeks of January 10, 17, 24, 31, February 7, 14, 2011. PLACE: Commissioners' Conference Room,...

  7. 76 FR 62868 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-11

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Week of October 10, 2011. PLACE: Commissioners' Conference Room, 11555 Rockville Pike,...

  8. 77 FR 3804 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission, [NRC-2012- 0002]. DATE: Week of January 30, 2012. PLACE: Commissioners' Conference Room, 11555...

  9. 76 FR 48919 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-09

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Weeks of August 8, 15, 22, 29, September 5, 12, 2011. PLACE: Commissioners' Conference Room,...

  10. 76 FR 41529 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-14

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission [NRC-2011- 0006]. DATE: Week of July 11, 2011. PLACE: Commissioners' Conference Room, 11555 Rockville...

  11. 76 FR 4393 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-25

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice Agency Holding the Meetings: Nuclear Regulatory Commission. Dates: Weeks of January 24, 31, February 7, 14, 21, 28, 2011. Place: Commissioners' Conference Room,...

  12. 77 FR 70488 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-26

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission DATES: Weeks of November 26, December 3, 10, 17, 24, 31, 2012 PLACE: Commissioners' Conference Room,...

  13. 76 FR 70779 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-15

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY: Agency Holding the Meetings: Nuclear Regulatory Commission. DATES: Weeks of November 14, 21, 28, December 5, 12, 19, 2011. Place: Commissioners'...

  14. 77 FR 67689 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Week of November 5, 2012. PLACE: Commissioners' Conference Room, 11555 Rockville Pike,...

  15. 75 FR 65674 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-26

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Weeks of October 25; November 1, 8, 15, 22, 29, 2010. PLACE: Commissioners' Conference Room,...

  16. 77 FR 304 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-04

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATES: Weeks of January 2, 9, 16, 23, 30, February 6, 2012. PLACE: Commissioners' Conference Room,...

  17. 76 FR 78952 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-20

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission, [NRC-2011- 0006]. DATE: Week of December 19, 2011. PLACE: Commissioners' Conference Room, 11555...

  18. 76 FR 64400 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-18

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission, [NRC-2011- 0006]. DATE: Weeks of October 17, 24, 31, November 7, 14, 21, 2011. PLACE:...

  19. 76 FR 11525 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORTY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATES: Week of February 28, 2011. PLACE: Commissioners' Conference Room, 11555 Rockville Pike,...

  20. 75 FR 67408 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-02

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice Agency Holding the Meetings: Nuclear Regulatory Commission. Date: Weeks of November 1, 8, 15, 22, 29, December 6, 2010. Place: Commissioners' Conference Room,...

  1. 75 FR 68630 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-08

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice Agency Holding the Meetings: Nuclear Regulatory Commission. Date: Week of November 1, 2010. Place: Commissioners' Conference Room, 11555 Rockville Pike,...

  2. 75 FR 59749 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice Agency Holding The Meetings: Nuclear Regulatory Commission. DATES: Weeks of September 27, October 4, 11, 18, 25, and November 1, 2010. Place: Commissioners'...

  3. 76 FR 24540 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-02

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Week of April 25, 2011. PLACE: Commissioners' Conference Room, 11555 Rockville Pike,...

  4. 78 FR 127 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-02

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Weeks of December 31, 2012, January 7, 14, 21, 28, February 4, 2013. PLACE: Commissioners'...

  5. 77 FR 67838 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-14

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Weeks of November 12, 19, 26, December 3, 10, 17, 2012. PLACE: Commissioners' Conference Room,...

  6. 76 FR 66095 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-25

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission, [NRC-2011- 0006]. DATE: Weeks of October 24, 31, November 7, 14, 21, 28, 2011. PLACE:...

  7. 76 FR 6837 - Sunshine Federal Register Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-08

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Sunshine Federal Register Notice AGENCY HOLDING THE MEETINGS: Nuclear Regulatory Commission. DATE: Weeks of February 7, 14, 21, 28, March 7, 14, 2011. PLACE: Commissioners' Conference Room,...

  8. Which Efficient Products Must Federal Agencies Buy

    SciTech Connect

    2010-08-24

    Fact sheet prepared by the U.S. Department of Energy (DOE) Federal Energy Management Program (FEMP) to help Federal agencies comply with FEMP Designated, Low Standby Power, ENERGY STAR Qualified, and Water Sense Labeled product purchasing requirements.

  9. California OCS Delegation Agreements Federal Register Notices

    EPA Pesticide Factsheets

    These federal register notices notify to the public that EPA has delegated authority to the agencies in the Federal Register Notices for sources within the 25 nautical miles of California's seaward boundary.

  10. 78 FR 13395 - Federal Aviation Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-27

    ... Federal Aviation Administration Notice of Availability of Draft Alaska National Interest Lands Conservation Act (ANILCA) Section 810 Subsistence Evaluation. AGENCY: Federal Aviation Administration (FAA... Aviation Administration, Airports Division, 222 West 7th Avenue, Box 14, Anchorage, AK 99513. 5....

  11. Federal Funding Accountability and Transparency Act

    EPA Pesticide Factsheets

    Public Law 109-282, the Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), requires disclosure of all entities and organizations receiving Federal funds through a single publicly accessible website.

  12. Federal Agency Hazardous Waste Compliance Docket

    EPA Pesticide Factsheets

    The Federal Agency Hazardous Waste Compliance Docket contains information reported to EPA by federal facilities that manage hazardous waste or from which hazardous substances, pollutants, or contaminants have been - or may be - released.

  13. Characteristics and Pay of Federal Civilian Employees

    DTIC Science & Technology

    2007-03-01

    Law Enforcement Officers (August 2005), Comparing the Pay of Federal and Nonprofit Executives: An Update (July 2003), Measuring Differences Between...Federal and Private Pay (November 2002), and Changes in Federal Civilian Employment: An Update (May 2001).In this paper, three general areas are...implement the basic civil service principle of equal pay for substantially equal work by assigning federal jobs to specific grades and steps on the

  14. The Economics of the Federal Budget Deficit

    DTIC Science & Technology

    2007-01-24

    Order Code RL31235 The Economics of the Federal Budget Deficit Updated January 24, 2007 Brian W. Cashell Specialist in Quantitative Economics...number. 1. REPORT DATE 24 JAN 2007 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE The Economics of the Federal Budget Deficit ...Prescribed by ANSI Std Z39-18 The Economics of the Federal Budget Deficit Summary The Congressional Budget Office (CBO) estimates that the federal

  15. Federal Wind Energy Research Program

    SciTech Connect

    Not Available

    1991-10-01

    The Office of Program Analysis (OPA) undertook an assessment of 55 research projects sponsored by the Federal Wind Energy Research Program. This report summarizes the results of that review. In accordance with statue and policy guidance, the program's research has targeted the sciences of wind turbine dynamics and the development of advanced components and systems. Wind turbine research has focused on atmospheric fluid dynamics, aerodynamics, and structural dynamics. Rating factors including project scientific and technical merit, appropriateness and level of innovation of the technical approach, quality of the project team, productivity, and probable impact on the program's mission. Each project was also given an overall evaluation supported with written comments. 1 fig.

  16. Federal Facility Agreement progress report

    SciTech Connect

    Not Available

    1993-10-01

    The (SRS) Federal Facility Agreement (FFA) was made effective by the US. Environmental Protection Agency Region IV (EPA) on August 16, 1993. To meet the reporting requirements in Section XXV of the Agreement, the FFA Progress Report was developed. The FFA Progress Report is the first of a series of quarterly progress reports to be prepared by the SRS. As such this report describes the information and action taken to September 30, 1993 on the SRS units identified for investigation and remediation in the Agreement. This includes; rubble pits, runoff basins, retention basin, seepage basin, burning pits, H-Area Tank 16, and spill areas.

  17. 10 CFR 961.5 - Federal agencies.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Federal agencies. 961.5 Section 961.5 Energy DEPARTMENT OF ENERGY STANDARD CONTRACT FOR DISPOSAL OF SPENT NUCLEAR FUEL AND/OR HIGH-LEVEL RADIOACTIVE WASTE General § 961.5 Federal agencies. Federal agencies or departments requiring DOE's disposal services for SNF...

  18. 10 CFR 961.5 - Federal agencies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Federal agencies. 961.5 Section 961.5 Energy DEPARTMENT OF ENERGY STANDARD CONTRACT FOR DISPOSAL OF SPENT NUCLEAR FUEL AND/OR HIGH-LEVEL RADIOACTIVE WASTE General § 961.5 Federal agencies. Federal agencies or departments requiring DOE's disposal services for SNF...

  19. 10 CFR 961.5 - Federal agencies.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Federal agencies. 961.5 Section 961.5 Energy DEPARTMENT OF ENERGY STANDARD CONTRACT FOR DISPOSAL OF SPENT NUCLEAR FUEL AND/OR HIGH-LEVEL RADIOACTIVE WASTE General § 961.5 Federal agencies. Federal agencies or departments requiring DOE's disposal services for SNF...

  20. 10 CFR 961.5 - Federal agencies.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Federal agencies. 961.5 Section 961.5 Energy DEPARTMENT OF ENERGY STANDARD CONTRACT FOR DISPOSAL OF SPENT NUCLEAR FUEL AND/OR HIGH-LEVEL RADIOACTIVE WASTE General § 961.5 Federal agencies. Federal agencies or departments requiring DOE's disposal services for SNF...

  1. Federal Employment of People with Disabilities

    ERIC Educational Resources Information Center

    Domzal, Christine

    2009-01-01

    The purpose of this paper is to examine the status of employment of people with disabilities in the Federal Government and to make recommendations for improving federal hiring and advancement of employees with disabilities. The paper summarizes the legal authorities and policy guidance, the responsibilities of various federal agencies charged with…

  2. 36 CFR 1253.8 - Federal Register.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Federal Register. 1253.8... AVAILABILITY AND USE LOCATION OF NARA FACILITIES AND HOURS OF USE § 1253.8 Federal Register. The location and business hours of the Office of the Federal Register are posted at http://www.archives.gov, and codified...

  3. 36 CFR 1253.8 - Federal Register.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Federal Register. 1253.8... AVAILABILITY AND USE LOCATION OF NARA FACILITIES AND HOURS OF USE § 1253.8 Federal Register. The location and business hours of the Office of the Federal Register are posted at http://www.archives.gov, and codified...

  4. 36 CFR 1253.8 - Federal Register.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Federal Register. 1253.8... AVAILABILITY AND USE LOCATION OF NARA FACILITIES AND HOURS OF USE § 1253.8 Federal Register. The location and business hours of the Office of the Federal Register are posted at http://www.archives.gov, and codified...

  5. 36 CFR 1253.8 - Federal Register.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Federal Register. 1253.8... AVAILABILITY AND USE LOCATION OF NARA FACILITIES AND HOURS OF USE § 1253.8 Federal Register. The location and business hours of the Office of the Federal Register are posted at http://www.archives.gov, and codified...

  6. The Federal Role in Postsecondary Education.

    ERIC Educational Resources Information Center

    Hodgkinson, Virginia A.

    The federal role in postsecondary education since 1787 is traced. Attention is directed to the types of indirect federal support toward postsecondary education until the first Higher Education Act of 1965, and the kinds of national priorities served by the current federal role in postsecondary education. Future projections and the implications of…

  7. 75 FR 61552 - Federal Railroad Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... Federal Railroad Administration Notice of Informational Filing In accordance with Section 236.913 of Title 49 of the Code of Federal Regulations (CFR), notice is hereby given that the Federal Railroad Administration (FRA) has received an informational filing from the Northeast Illinois Regional Commuter...

  8. Survey of Federal Libraries; Fiscal Year 1972.

    ERIC Educational Resources Information Center

    National Center for Educational Statistics (DHEW/OE), Washington, DC.

    The fourth study of federal libraries provided the first nearly complete statistical survey of all federal libraries in the continental United States and overseas. It was anticipated that the results of the study could serve as a landmark for future federal planning and as a guide for the library community in responding to related activities on…

  9. Federal Student Aid Annual Report, 2010

    ERIC Educational Resources Information Center

    US Department of Education, 2010

    2010-01-01

    This paper presents the Federal Student Aid Annual Report for 2010. Federal Student Aid experienced an extraordinary year in 2010. The passage and enactment of the Health Care and Education Reconciliation Act of 2010 ushered in sweeping reforms to the federal student financial assistance programs, resulting in tens of billions of dollars in…

  10. 13 CFR 314.5 - Federal Share.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Federal Share. 314.5 Section 314.5 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE PROPERTY General § 314.5 Federal Share. (a) For purposes of this part, “Federal Share” means that portion of the...

  11. 78 FR 25524 - Federal Aviation Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-01

    ... TRANSPORTATION Federal Aviation Administration Notice of Request To Release Airport Property AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of Intent to Rule on Request to Release Airport Property..., Airports Compliance Specialist, Federal Aviation Administration, Airports Division, ACE- 610C, 901...

  12. 23 CFR 750.305 - Federal participation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Federal participation. 750.305 Section 750.305 Highways... participation. (a) Federal funds may participate in: (1) Payments made to a sign owner for his right, title and... personnel on a force account basis or by contract. Documentation for Federal participation in such...

  13. 23 CFR 750.305 - Federal participation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Federal participation. 750.305 Section 750.305 Highways... participation. (a) Federal funds may participate in: (1) Payments made to a sign owner for his right, title and... personnel on a force account basis or by contract. Documentation for Federal participation in such...

  14. 23 CFR 652.9 - Federal participation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Federal participation. 652.9 Section 652.9 Highways... AND BICYCLE ACCOMMODATIONS AND PROJECTS § 652.9 Federal participation. (a) Independent walkway... exceeded. (b) Specific eligibility requirements for Federal-aid participation in independent...

  15. 23 CFR 652.9 - Federal participation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Federal participation. 652.9 Section 652.9 Highways... AND BICYCLE ACCOMMODATIONS AND PROJECTS § 652.9 Federal participation. (a) Independent walkway... exceeded. (b) Specific eligibility requirements for Federal-aid participation in independent...

  16. 29 CFR 4.107 - Federal contracts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 1 2014-07-01 2013-07-01 true Federal contracts. 4.107 Section 4.107 Labor Office of the Secretary of Labor LABOR STANDARDS FOR FEDERAL SERVICE CONTRACTS Application of the McNamara-O'Hara Service Contract Act Agencies Whose Contracts May Be Covered § 4.107 Federal contracts. (a) Section 2(a) of the...

  17. 23 CFR 652.9 - Federal participation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 23 Highways 1 2012-04-01 2012-04-01 false Federal participation. 652.9 Section 652.9 Highways... AND BICYCLE ACCOMMODATIONS AND PROJECTS § 652.9 Federal participation. (a) Independent walkway... exceeded. (b) Specific eligibility requirements for Federal-aid participation in independent...

  18. 23 CFR 772.15 - Federal participation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 23 Highways 1 2014-04-01 2014-04-01 false Federal participation. 772.15 Section 772.15 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT PROCEDURES FOR ABATEMENT OF HIGHWAY TRAFFIC NOISE AND CONSTRUCTION NOISE § 772.15 Federal participation. (a) Type I...

  19. 23 CFR 750.305 - Federal participation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 23 Highways 1 2012-04-01 2012-04-01 false Federal participation. 750.305 Section 750.305 Highways... participation. (a) Federal funds may participate in: (1) Payments made to a sign owner for his right, title and... personnel on a force account basis or by contract. Documentation for Federal participation in such...

  20. 23 CFR 772.15 - Federal participation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 23 Highways 1 2012-04-01 2012-04-01 false Federal participation. 772.15 Section 772.15 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RIGHT-OF-WAY AND ENVIRONMENT PROCEDURES FOR ABATEMENT OF HIGHWAY TRAFFIC NOISE AND CONSTRUCTION NOISE § 772.15 Federal participation. (a) Type I...